CA2290426A1 - Recepteurs du facteur neurotrophique derive de lignes de cellules gliales - Google Patents
Recepteurs du facteur neurotrophique derive de lignes de cellules gliales Download PDFInfo
- Publication number
- CA2290426A1 CA2290426A1 CA002290426A CA2290426A CA2290426A1 CA 2290426 A1 CA2290426 A1 CA 2290426A1 CA 002290426 A CA002290426 A CA 002290426A CA 2290426 A CA2290426 A CA 2290426A CA 2290426 A1 CA2290426 A1 CA 2290426A1
- Authority
- CA
- Canada
- Prior art keywords
- gdnf
- cells
- ret
- receptor
- receptors
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 102000004216 Glial cell line-derived neurotrophic factor receptors Human genes 0.000 title description 103
- 108090000722 Glial cell line-derived neurotrophic factor receptors Proteins 0.000 title description 103
- 150000001875 compounds Chemical class 0.000 claims description 16
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 11
- 102000039446 nucleic acids Human genes 0.000 claims description 9
- 108020004707 nucleic acids Proteins 0.000 claims description 9
- 150000007523 nucleic acids Chemical class 0.000 claims description 9
- 108091010837 Glial cell line-derived neurotrophic factor Proteins 0.000 abstract description 383
- 102000034615 Glial cell line-derived neurotrophic factor Human genes 0.000 abstract description 371
- 230000014509 gene expression Effects 0.000 abstract description 80
- 238000012512 characterization method Methods 0.000 abstract description 10
- 238000002955 isolation Methods 0.000 abstract description 9
- 230000001413 cellular effect Effects 0.000 abstract description 4
- 238000002360 preparation method Methods 0.000 abstract description 2
- 210000004027 cell Anatomy 0.000 description 414
- 102000005962 receptors Human genes 0.000 description 128
- 108020003175 receptors Proteins 0.000 description 128
- 108010001648 Proto-Oncogene Proteins c-ret Proteins 0.000 description 107
- 102000000813 Proto-Oncogene Proteins c-ret Human genes 0.000 description 103
- 108020004999 messenger RNA Proteins 0.000 description 85
- 230000027455 binding Effects 0.000 description 65
- 210000002569 neuron Anatomy 0.000 description 65
- 108090000623 proteins and genes Proteins 0.000 description 62
- 230000026731 phosphorylation Effects 0.000 description 56
- 238000006366 phosphorylation reaction Methods 0.000 description 56
- 102000004169 proteins and genes Human genes 0.000 description 48
- 235000018102 proteins Nutrition 0.000 description 47
- 239000002299 complementary DNA Substances 0.000 description 43
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 37
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 37
- 241000699666 Mus <mouse, genus> Species 0.000 description 36
- 239000003446 ligand Substances 0.000 description 36
- 230000004083 survival effect Effects 0.000 description 30
- 238000011282 treatment Methods 0.000 description 30
- 210000004556 brain Anatomy 0.000 description 26
- 238000004132 cross linking Methods 0.000 description 26
- 230000000694 effects Effects 0.000 description 26
- 210000002161 motor neuron Anatomy 0.000 description 26
- 238000000034 method Methods 0.000 description 24
- 210000003523 substantia nigra Anatomy 0.000 description 24
- 210000001609 raphe nuclei Anatomy 0.000 description 23
- 108010007457 Extracellular Signal-Regulated MAP Kinases Proteins 0.000 description 21
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 20
- 102000007665 Extracellular Signal-Regulated MAP Kinases Human genes 0.000 description 20
- 210000002950 fibroblast Anatomy 0.000 description 20
- 210000003734 kidney Anatomy 0.000 description 20
- 230000002889 sympathetic effect Effects 0.000 description 19
- 108010025020 Nerve Growth Factor Proteins 0.000 description 18
- 210000001035 gastrointestinal tract Anatomy 0.000 description 18
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 17
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 17
- 101000876610 Dictyostelium discoideum Extracellular signal-regulated kinase 2 Proteins 0.000 description 16
- 101001052493 Homo sapiens Mitogen-activated protein kinase 1 Proteins 0.000 description 16
- 102100024193 Mitogen-activated protein kinase 1 Human genes 0.000 description 16
- 206010029260 Neuroblastoma Diseases 0.000 description 16
- 108010071563 Proto-Oncogene Proteins c-fos Proteins 0.000 description 16
- 102000007568 Proto-Oncogene Proteins c-fos Human genes 0.000 description 16
- 230000003902 lesion Effects 0.000 description 16
- 230000004044 response Effects 0.000 description 16
- 102000015336 Nerve Growth Factor Human genes 0.000 description 15
- 238000004458 analytical method Methods 0.000 description 15
- 238000009396 hybridization Methods 0.000 description 15
- 229940053128 nerve growth factor Drugs 0.000 description 15
- 230000001537 neural effect Effects 0.000 description 15
- 108700020796 Oncogene Proteins 0.000 description 14
- 230000004069 differentiation Effects 0.000 description 13
- 210000005064 dopaminergic neuron Anatomy 0.000 description 13
- 238000001727 in vivo Methods 0.000 description 13
- 238000002372 labelling Methods 0.000 description 13
- 239000002609 medium Substances 0.000 description 13
- 230000002474 noradrenergic effect Effects 0.000 description 13
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- 238000002474 experimental method Methods 0.000 description 12
- 239000000523 sample Substances 0.000 description 12
- 230000019491 signal transduction Effects 0.000 description 12
- 210000001519 tissue Anatomy 0.000 description 12
- 230000004913 activation Effects 0.000 description 11
- 238000001114 immunoprecipitation Methods 0.000 description 11
- DIVDFFZHCJEHGG-UHFFFAOYSA-N oxidopamine Chemical compound NCCC1=CC(O)=C(O)C=C1O DIVDFFZHCJEHGG-UHFFFAOYSA-N 0.000 description 11
- 239000013612 plasmid Substances 0.000 description 11
- 210000002966 serum Anatomy 0.000 description 11
- 238000001262 western blot Methods 0.000 description 11
- 239000013592 cell lysate Substances 0.000 description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
- 239000000284 extract Substances 0.000 description 10
- 239000003102 growth factor Substances 0.000 description 10
- 239000006166 lysate Substances 0.000 description 10
- 238000001890 transfection Methods 0.000 description 10
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- 102000001708 Protein Isoforms Human genes 0.000 description 9
- 108010029485 Protein Isoforms Proteins 0.000 description 9
- 229920002684 Sepharose Polymers 0.000 description 9
- 230000004071 biological effect Effects 0.000 description 9
- 238000011161 development Methods 0.000 description 9
- 230000018109 developmental process Effects 0.000 description 9
- ZWIBGKZDAWNIFC-UHFFFAOYSA-N disuccinimidyl suberate Chemical compound O=C1CCC(=O)N1OC(=O)CCCCCCC(=O)ON1C(=O)CCC1=O ZWIBGKZDAWNIFC-UHFFFAOYSA-N 0.000 description 9
- 239000000499 gel Substances 0.000 description 9
- 210000000627 locus coeruleus Anatomy 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- 210000003098 myoblast Anatomy 0.000 description 9
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 8
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 8
- 238000003556 assay Methods 0.000 description 8
- 238000000211 autoradiogram Methods 0.000 description 8
- 230000008512 biological response Effects 0.000 description 8
- 239000013553 cell monolayer Substances 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 230000006870 function Effects 0.000 description 8
- 238000007901 in situ hybridization Methods 0.000 description 8
- 230000007246 mechanism Effects 0.000 description 8
- 239000013615 primer Substances 0.000 description 8
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 8
- 210000000278 spinal cord Anatomy 0.000 description 8
- 230000001052 transient effect Effects 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 7
- 241000283973 Oryctolagus cuniculus Species 0.000 description 7
- 230000009471 action Effects 0.000 description 7
- 235000001014 amino acid Nutrition 0.000 description 7
- 238000000376 autoradiography Methods 0.000 description 7
- 210000000349 chromosome Anatomy 0.000 description 7
- 239000003599 detergent Substances 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
- 231100000673 dose–response relationship Toxicity 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 210000005216 enteric neuron Anatomy 0.000 description 7
- 230000012010 growth Effects 0.000 description 7
- 238000011065 in-situ storage Methods 0.000 description 7
- 210000003292 kidney cell Anatomy 0.000 description 7
- 210000004072 lung Anatomy 0.000 description 7
- 210000003205 muscle Anatomy 0.000 description 7
- 239000002773 nucleotide Substances 0.000 description 7
- 125000003729 nucleotide group Chemical group 0.000 description 7
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 7
- 230000011664 signaling Effects 0.000 description 7
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 7
- 239000013598 vector Substances 0.000 description 7
- 102000014914 Carrier Proteins Human genes 0.000 description 6
- 238000002965 ELISA Methods 0.000 description 6
- 206010073148 Multiple endocrine neoplasia type 2A Diseases 0.000 description 6
- 102000052575 Proto-Oncogene Human genes 0.000 description 6
- 108700020978 Proto-Oncogene Proteins 0.000 description 6
- 150000001413 amino acids Chemical class 0.000 description 6
- 108091008324 binding proteins Proteins 0.000 description 6
- 210000003169 central nervous system Anatomy 0.000 description 6
- 230000000875 corresponding effect Effects 0.000 description 6
- 238000009826 distribution Methods 0.000 description 6
- 230000003291 dopaminomimetic effect Effects 0.000 description 6
- 229930004094 glycosylphosphatidylinositol Natural products 0.000 description 6
- 238000011534 incubation Methods 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- 230000037361 pathway Effects 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 102000035025 signaling receptors Human genes 0.000 description 6
- 108091005475 signaling receptors Proteins 0.000 description 6
- 230000003827 upregulation Effects 0.000 description 6
- 241000772415 Neovison vison Species 0.000 description 5
- 102000004230 Neurotrophin 3 Human genes 0.000 description 5
- 108090000742 Neurotrophin 3 Proteins 0.000 description 5
- 238000000636 Northern blotting Methods 0.000 description 5
- 108091000080 Phosphotransferase Proteins 0.000 description 5
- 108091000117 Tyrosine 3-Monooxygenase Proteins 0.000 description 5
- 102000048218 Tyrosine 3-monooxygenases Human genes 0.000 description 5
- 238000010367 cloning Methods 0.000 description 5
- 210000002919 epithelial cell Anatomy 0.000 description 5
- 108700025906 fos Genes Proteins 0.000 description 5
- 239000012634 fragment Substances 0.000 description 5
- 210000004754 hybrid cell Anatomy 0.000 description 5
- 230000003834 intracellular effect Effects 0.000 description 5
- 210000001161 mammalian embryo Anatomy 0.000 description 5
- 229940032018 neurotrophin 3 Drugs 0.000 description 5
- 102000020233 phosphotransferase Human genes 0.000 description 5
- 210000004129 prosencephalon Anatomy 0.000 description 5
- 238000012216 screening Methods 0.000 description 5
- 230000000862 serotonergic effect Effects 0.000 description 5
- 239000012679 serum free medium Substances 0.000 description 5
- 241000894007 species Species 0.000 description 5
- 230000000638 stimulation Effects 0.000 description 5
- 238000013518 transcription Methods 0.000 description 5
- 230000035897 transcription Effects 0.000 description 5
- 230000009466 transformation Effects 0.000 description 5
- 102000007350 Bone Morphogenetic Proteins Human genes 0.000 description 4
- 108010007726 Bone Morphogenetic Proteins Proteins 0.000 description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- 241000283707 Capra Species 0.000 description 4
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
- 208000032612 Glial tumor Diseases 0.000 description 4
- 206010018338 Glioma Diseases 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 239000000020 Nitrocellulose Substances 0.000 description 4
- 208000018737 Parkinson disease Diseases 0.000 description 4
- 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 4
- 108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 4
- 101100068253 Rattus norvegicus Gdnf gene Proteins 0.000 description 4
- 125000000539 amino acid group Chemical group 0.000 description 4
- 230000003042 antagnostic effect Effects 0.000 description 4
- 230000002788 anti-peptide Effects 0.000 description 4
- 230000000692 anti-sense effect Effects 0.000 description 4
- 108010079292 betaglycan Proteins 0.000 description 4
- 229940112869 bone morphogenetic protein Drugs 0.000 description 4
- 210000005056 cell body Anatomy 0.000 description 4
- VDQQXEISLMTGAB-UHFFFAOYSA-N chloramine T Chemical compound [Na+].CC1=CC=C(S(=O)(=O)[N-]Cl)C=C1 VDQQXEISLMTGAB-UHFFFAOYSA-N 0.000 description 4
- 230000009146 cooperative binding Effects 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 239000013613 expression plasmid Substances 0.000 description 4
- 230000001605 fetal effect Effects 0.000 description 4
- 238000002509 fluorescent in situ hybridization Methods 0.000 description 4
- 230000004927 fusion Effects 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 229940090044 injection Drugs 0.000 description 4
- 210000004185 liver Anatomy 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 210000004379 membrane Anatomy 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 210000001259 mesencephalon Anatomy 0.000 description 4
- 230000031864 metaphase Effects 0.000 description 4
- 239000000178 monomer Substances 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- 210000000653 nervous system Anatomy 0.000 description 4
- 229920001220 nitrocellulos Polymers 0.000 description 4
- 230000003076 paracrine Effects 0.000 description 4
- 208000028591 pheochromocytoma Diseases 0.000 description 4
- 229920001184 polypeptide Polymers 0.000 description 4
- 230000003389 potentiating effect Effects 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 102000004196 processed proteins & peptides Human genes 0.000 description 4
- 230000004043 responsiveness Effects 0.000 description 4
- 210000000717 sertoli cell Anatomy 0.000 description 4
- 210000000130 stem cell Anatomy 0.000 description 4
- 230000002459 sustained effect Effects 0.000 description 4
- 230000002463 transducing effect Effects 0.000 description 4
- 238000010361 transduction Methods 0.000 description 4
- 230000026683 transduction Effects 0.000 description 4
- 230000001228 trophic effect Effects 0.000 description 4
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 4
- GZCWLCBFPRFLKL-UHFFFAOYSA-N 1-prop-2-ynoxypropan-2-ol Chemical compound CC(O)COCC#C GZCWLCBFPRFLKL-UHFFFAOYSA-N 0.000 description 3
- 101150090724 3 gene Proteins 0.000 description 3
- 102000013563 Acid Phosphatase Human genes 0.000 description 3
- 108010051457 Acid Phosphatase Proteins 0.000 description 3
- 241000282693 Cercopithecidae Species 0.000 description 3
- 108020004705 Codon Proteins 0.000 description 3
- 102000008186 Collagen Human genes 0.000 description 3
- 108010035532 Collagen Proteins 0.000 description 3
- 108020004635 Complementary DNA Proteins 0.000 description 3
- 206010010539 Congenital megacolon Diseases 0.000 description 3
- 239000004971 Cross linker Substances 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 241000238631 Hexapoda Species 0.000 description 3
- 208000004592 Hirschsprung disease Diseases 0.000 description 3
- 101000997829 Homo sapiens Glial cell line-derived neurotrophic factor Proteins 0.000 description 3
- 101000579425 Homo sapiens Proto-oncogene tyrosine-protein kinase receptor Ret Proteins 0.000 description 3
- 102000043136 MAP kinase family Human genes 0.000 description 3
- 241001529936 Murinae Species 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- 102000007072 Nerve Growth Factors Human genes 0.000 description 3
- 108010076504 Protein Sorting Signals Proteins 0.000 description 3
- 102100028286 Proto-oncogene tyrosine-protein kinase receptor Ret Human genes 0.000 description 3
- 210000004100 adrenal gland Anatomy 0.000 description 3
- 230000003305 autocrine Effects 0.000 description 3
- 230000035578 autophosphorylation Effects 0.000 description 3
- 239000011324 bead Substances 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 229940098773 bovine serum albumin Drugs 0.000 description 3
- 230000007910 cell fusion Effects 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 238000010382 chemical cross-linking Methods 0.000 description 3
- 229920001436 collagen Polymers 0.000 description 3
- 239000012228 culture supernatant Substances 0.000 description 3
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 238000006073 displacement reaction Methods 0.000 description 3
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical class NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 3
- 229960003638 dopamine Drugs 0.000 description 3
- 239000013604 expression vector Substances 0.000 description 3
- 210000000609 ganglia Anatomy 0.000 description 3
- 102000052654 human GDNF Human genes 0.000 description 3
- 238000004191 hydrophobic interaction chromatography Methods 0.000 description 3
- 238000002649 immunization Methods 0.000 description 3
- 238000002991 immunohistochemical analysis Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 230000003278 mimic effect Effects 0.000 description 3
- 230000037230 mobility Effects 0.000 description 3
- 210000001577 neostriatum Anatomy 0.000 description 3
- 230000004770 neurodegeneration Effects 0.000 description 3
- 239000003900 neurotrophic factor Substances 0.000 description 3
- 210000004940 nucleus Anatomy 0.000 description 3
- 210000002826 placenta Anatomy 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 238000000159 protein binding assay Methods 0.000 description 3
- 238000011002 quantification Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 210000001550 testis Anatomy 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 230000009261 transgenic effect Effects 0.000 description 3
- 238000002054 transplantation Methods 0.000 description 3
- 210000000427 trigeminal ganglion Anatomy 0.000 description 3
- 102000047459 trkC Receptor Human genes 0.000 description 3
- 108010064892 trkC Receptor Proteins 0.000 description 3
- 210000000626 ureter Anatomy 0.000 description 3
- UBWXUGDQUBIEIZ-UHFFFAOYSA-N (13-methyl-3-oxo-2,6,7,8,9,10,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-17-yl) 3-phenylpropanoate Chemical compound CC12CCC(C3CCC(=O)C=C3CC3)C3C1CCC2OC(=O)CCC1=CC=CC=C1 UBWXUGDQUBIEIZ-UHFFFAOYSA-N 0.000 description 2
- 108010059616 Activins Proteins 0.000 description 2
- 102000005606 Activins Human genes 0.000 description 2
- 229920000936 Agarose Polymers 0.000 description 2
- 101710132601 Capsid protein Proteins 0.000 description 2
- 108091035707 Consensus sequence Proteins 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 102000001301 EGF receptor Human genes 0.000 description 2
- 108060006698 EGF receptor Proteins 0.000 description 2
- 102100037241 Endoglin Human genes 0.000 description 2
- 108010036395 Endoglin Proteins 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 2
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 2
- 241000287828 Gallus gallus Species 0.000 description 2
- 101000712674 Homo sapiens TGF-beta receptor type-1 Proteins 0.000 description 2
- 101000712669 Homo sapiens TGF-beta receptor type-2 Proteins 0.000 description 2
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 2
- 108700002232 Immediate-Early Genes Proteins 0.000 description 2
- 108090001090 Lectins Proteins 0.000 description 2
- 102000004856 Lectins Human genes 0.000 description 2
- 108091054455 MAP kinase family Proteins 0.000 description 2
- 230000004988 N-glycosylation Effects 0.000 description 2
- 102000016979 Other receptors Human genes 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- 208000027089 Parkinsonian disease Diseases 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- 108700025832 Serum Response Element Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 102100033456 TGF-beta receptor type-1 Human genes 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 102000040945 Transcription factor Human genes 0.000 description 2
- 108091023040 Transcription factor Proteins 0.000 description 2
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 2
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 2
- 102100033663 Transforming growth factor beta receptor type 3 Human genes 0.000 description 2
- 108010003205 Vasoactive Intestinal Peptide Proteins 0.000 description 2
- 102400000015 Vasoactive intestinal peptide Human genes 0.000 description 2
- 239000000488 activin Substances 0.000 description 2
- 210000004404 adrenal cortex Anatomy 0.000 description 2
- 210000001943 adrenal medulla Anatomy 0.000 description 2
- 239000011543 agarose gel Substances 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 238000000540 analysis of variance Methods 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- RIIWUGSYXOBDMC-UHFFFAOYSA-N benzene-1,2-diamine;hydron;dichloride Chemical compound Cl.Cl.NC1=CC=CC=C1N RIIWUGSYXOBDMC-UHFFFAOYSA-N 0.000 description 2
- 239000012148 binding buffer Substances 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 238000002737 cell proliferation kit Methods 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 210000002932 cholinergic neuron Anatomy 0.000 description 2
- 238000012761 co-transfection Methods 0.000 description 2
- 238000012875 competitive assay Methods 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 235000018417 cysteine Nutrition 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- 239000000539 dimer Substances 0.000 description 2
- 238000006471 dimerization reaction Methods 0.000 description 2
- 230000007783 downstream signaling Effects 0.000 description 2
- 238000009510 drug design Methods 0.000 description 2
- 238000004520 electroporation Methods 0.000 description 2
- 230000001815 facial effect Effects 0.000 description 2
- 210000003754 fetus Anatomy 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 229940126864 fibroblast growth factor Drugs 0.000 description 2
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 2
- 230000002518 glial effect Effects 0.000 description 2
- 230000013595 glycosylation Effects 0.000 description 2
- 238000006206 glycosylation reaction Methods 0.000 description 2
- YQOKLYTXVFAUCW-UHFFFAOYSA-N guanidine;isothiocyanic acid Chemical compound N=C=S.NC(N)=N YQOKLYTXVFAUCW-UHFFFAOYSA-N 0.000 description 2
- 210000001320 hippocampus Anatomy 0.000 description 2
- 210000003917 human chromosome Anatomy 0.000 description 2
- 210000004408 hybridoma Anatomy 0.000 description 2
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
- 238000003119 immunoblot Methods 0.000 description 2
- 239000012133 immunoprecipitate Substances 0.000 description 2
- 210000004283 incisor Anatomy 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 210000000936 intestine Anatomy 0.000 description 2
- 230000004068 intracellular signaling Effects 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- VBUWHHLIZKOSMS-RIWXPGAOSA-N invicorp Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)C(C)C)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 VBUWHHLIZKOSMS-RIWXPGAOSA-N 0.000 description 2
- 239000002523 lectin Substances 0.000 description 2
- 239000012139 lysis buffer Substances 0.000 description 2
- 210000004245 medial forebrain bundle Anatomy 0.000 description 2
- 238000001000 micrograph Methods 0.000 description 2
- 230000002297 mitogenic effect Effects 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 210000001178 neural stem cell Anatomy 0.000 description 2
- 208000015122 neurodegenerative disease Diseases 0.000 description 2
- 210000004498 neuroglial cell Anatomy 0.000 description 2
- 230000004031 neuronal differentiation Effects 0.000 description 2
- 230000000508 neurotrophic effect Effects 0.000 description 2
- 230000009871 nonspecific binding Effects 0.000 description 2
- 231100000590 oncogenic Toxicity 0.000 description 2
- 230000002246 oncogenic effect Effects 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
- 238000011458 pharmacological treatment Methods 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- DCWXELXMIBXGTH-UHFFFAOYSA-N phosphotyrosine Chemical compound OC(=O)C(N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-UHFFFAOYSA-N 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 108010041634 preprotachykinin Proteins 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- KIDHWZJUCRJVML-UHFFFAOYSA-N putrescine Chemical compound NCCCCN KIDHWZJUCRJVML-UHFFFAOYSA-N 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 210000001525 retina Anatomy 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 238000009738 saturating Methods 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 239000004017 serum-free culture medium Substances 0.000 description 2
- 230000007727 signaling mechanism Effects 0.000 description 2
- 210000000813 small intestine Anatomy 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 210000003594 spinal ganglia Anatomy 0.000 description 2
- 210000000273 spinal nerve root Anatomy 0.000 description 2
- 210000004989 spleen cell Anatomy 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- FRGKKTITADJNOE-UHFFFAOYSA-N sulfanyloxyethane Chemical compound CCOS FRGKKTITADJNOE-UHFFFAOYSA-N 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 2
- 210000005239 tubule Anatomy 0.000 description 2
- 108091005990 tyrosine-phosphorylated proteins Proteins 0.000 description 2
- 241000701447 unidentified baculovirus Species 0.000 description 2
- 230000002620 ureteric effect Effects 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- FXYPGCIGRDZWNR-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-[[3-(2,5-dioxopyrrolidin-1-yl)oxy-3-oxopropyl]disulfanyl]propanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCSSCCC(=O)ON1C(=O)CCC1=O FXYPGCIGRDZWNR-UHFFFAOYSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- TVZGACDUOSZQKY-LBPRGKRZSA-N 4-aminofolic acid Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 TVZGACDUOSZQKY-LBPRGKRZSA-N 0.000 description 1
- 102000015936 AP-1 transcription factor Human genes 0.000 description 1
- 108050004195 AP-1 transcription factor Proteins 0.000 description 1
- 108010052946 Activin Receptors Proteins 0.000 description 1
- 102000018918 Activin Receptors Human genes 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 108010087765 Antipain Proteins 0.000 description 1
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 1
- 206010002961 Aplasia Diseases 0.000 description 1
- 108010039627 Aprotinin Proteins 0.000 description 1
- 208000002109 Argyria Diseases 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 101100222854 Bacillus subtilis (strain 168) czcO gene Proteins 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 101710120271 Bone morphogenetic protein receptor type-1B Proteins 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 108010058699 Choline O-acetyltransferase Proteins 0.000 description 1
- 102100023460 Choline O-acetyltransferase Human genes 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 208000027205 Congenital disease Diseases 0.000 description 1
- 208000029767 Congenital, Hereditary, and Neonatal Diseases and Abnormalities Diseases 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- LXJXRIRHZLFYRP-VKHMYHEASA-N D-glyceraldehyde 3-phosphate Chemical compound O=C[C@H](O)COP(O)(O)=O LXJXRIRHZLFYRP-VKHMYHEASA-N 0.000 description 1
- 239000003155 DNA primer Substances 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- HCYAFALTSJYZDH-UHFFFAOYSA-N Desimpramine Chemical compound C1CC2=CC=CC=C2N(CCCNC)C2=CC=CC=C21 HCYAFALTSJYZDH-UHFFFAOYSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 101100015729 Drosophila melanogaster drk gene Proteins 0.000 description 1
- 239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 1
- 239000006145 Eagle's minimal essential medium Substances 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 102400001368 Epidermal growth factor Human genes 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- 101100127166 Escherichia coli (strain K12) kefB gene Proteins 0.000 description 1
- 201000006850 Familial medullary thyroid carcinoma Diseases 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 241001251094 Formica Species 0.000 description 1
- 101000993347 Gallus gallus Ciliary neurotrophic factor Proteins 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 1
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 1
- 101001109689 Homo sapiens Nuclear receptor subfamily 4 group A member 3 Proteins 0.000 description 1
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 102000001702 Intracellular Signaling Peptides and Proteins Human genes 0.000 description 1
- 108010068964 Intracellular Signaling Peptides and Proteins Proteins 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
- 241000282560 Macaca mulatta Species 0.000 description 1
- 208000037196 Medullary thyroid carcinoma Diseases 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 101100537961 Methanosarcina mazei (strain ATCC BAA-159 / DSM 3647 / Goe1 / Go1 / JCM 11833 / OCM 88) trkA2 gene Proteins 0.000 description 1
- 102000009664 Microtubule-Associated Proteins Human genes 0.000 description 1
- 108010020004 Microtubule-Associated Proteins Proteins 0.000 description 1
- 206010073149 Multiple endocrine neoplasia Type 2 Diseases 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- WUKZPHOXUVCQOR-UHFFFAOYSA-N N-(1-azabicyclo[2.2.2]octan-3-yl)-6-chloro-4-methyl-3-oxo-1,4-benzoxazine-8-carboxamide Chemical compound C1N(CC2)CCC2C1NC(=O)C1=CC(Cl)=CC2=C1OCC(=O)N2C WUKZPHOXUVCQOR-UHFFFAOYSA-N 0.000 description 1
- 102000007339 Nerve Growth Factor Receptors Human genes 0.000 description 1
- 108010032605 Nerve Growth Factor Receptors Proteins 0.000 description 1
- 102000008763 Neurofilament Proteins Human genes 0.000 description 1
- 108010088373 Neurofilament Proteins Proteins 0.000 description 1
- 108090000189 Neuropeptides Proteins 0.000 description 1
- 102000003797 Neuropeptides Human genes 0.000 description 1
- 102100021584 Neurturin Human genes 0.000 description 1
- 108010015406 Neurturin Proteins 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- 102000016978 Orphan receptors Human genes 0.000 description 1
- 108070000031 Orphan receptors Proteins 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 102000004590 Peripherins Human genes 0.000 description 1
- 108010003081 Peripherins Proteins 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- 102100027584 Protein c-Fos Human genes 0.000 description 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 108010067787 Proteoglycans Proteins 0.000 description 1
- 102000016611 Proteoglycans Human genes 0.000 description 1
- 239000005700 Putrescine Substances 0.000 description 1
- 239000012614 Q-Sepharose Substances 0.000 description 1
- 238000002123 RNA extraction Methods 0.000 description 1
- 239000013614 RNA sample Substances 0.000 description 1
- 101100496572 Rattus norvegicus C6 gene Proteins 0.000 description 1
- 102000006382 Ribonucleases Human genes 0.000 description 1
- 108010083644 Ribonucleases Proteins 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- LDEBVRIURYMKQS-WISUUJSJSA-N Ser-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H](N)CO LDEBVRIURYMKQS-WISUUJSJSA-N 0.000 description 1
- 102100034136 Serine/threonine-protein kinase receptor R3 Human genes 0.000 description 1
- 101710082813 Serine/threonine-protein kinase receptor R3 Proteins 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 102100033455 TGF-beta receptor type-2 Human genes 0.000 description 1
- 108010006785 Taq Polymerase Proteins 0.000 description 1
- 101710120037 Toxin CcdB Proteins 0.000 description 1
- 102000004338 Transferrin Human genes 0.000 description 1
- 108090000901 Transferrin Proteins 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 108010046516 Wheat Germ Agglutinins Proteins 0.000 description 1
- HMNZFMSWFCAGGW-XPWSMXQVSA-N [3-[hydroxy(2-hydroxyethoxy)phosphoryl]oxy-2-[(e)-octadec-9-enoyl]oxypropyl] (e)-octadec-9-enoate Chemical compound CCCCCCCC\C=C\CCCCCCCC(=O)OCC(COP(O)(=O)OCCO)OC(=O)CCCCCCC\C=C\CCCCCCCC HMNZFMSWFCAGGW-XPWSMXQVSA-N 0.000 description 1
- AZRNEVJSOSKAOC-VPHBQDTQSA-N [[(2r,3s,5r)-5-[5-[(e)-3-[6-[5-[(3as,4s,6ar)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]hexanoylamino]prop-1-enyl]-2,4-dioxopyrimidin-1-yl]-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound O1[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)C[C@@H]1N1C(=O)NC(=O)C(\C=C\CNC(=O)CCCCCNC(=O)CCCC[C@H]2[C@H]3NC(=O)N[C@H]3CS2)=C1 AZRNEVJSOSKAOC-VPHBQDTQSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 102000035181 adaptor proteins Human genes 0.000 description 1
- 108091005764 adaptor proteins Proteins 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 229960003896 aminopterin Drugs 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 230000019552 anatomical structure morphogenesis Effects 0.000 description 1
- 238000004873 anchoring Methods 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 238000005571 anion exchange chromatography Methods 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000003302 anti-idiotype Effects 0.000 description 1
- 230000000648 anti-parkinson Effects 0.000 description 1
- 229940019748 antifibrinolytic proteinase inhibitors Drugs 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- SDNYTAYICBFYFH-TUFLPTIASA-N antipain Chemical compound NC(N)=NCCC[C@@H](C=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 SDNYTAYICBFYFH-TUFLPTIASA-N 0.000 description 1
- 239000000939 antiparkinson agent Substances 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 229960004405 aprotinin Drugs 0.000 description 1
- 210000003050 axon Anatomy 0.000 description 1
- LZCZIHQBSCVGRD-UHFFFAOYSA-N benzenecarboximidamide;hydron;chloride Chemical compound [Cl-].NC(=[NH2+])C1=CC=CC=C1 LZCZIHQBSCVGRD-UHFFFAOYSA-N 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 239000011545 carbonate/bicarbonate buffer Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000011748 cell maturation Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 210000001638 cerebellum Anatomy 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 108700010039 chimeric receptor Proteins 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 238000010835 comparative analysis Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000003184 complementary RNA Substances 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 239000003636 conditioned culture medium Substances 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 210000005220 cytoplasmic tail Anatomy 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 229960003914 desipramine Drugs 0.000 description 1
- 230000034373 developmental growth involved in morphogenesis Effects 0.000 description 1
- 238000002050 diffraction method Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000003113 dilution method Methods 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 229940005482 dopamine injection Drugs 0.000 description 1
- 230000028436 dopamine uptake Effects 0.000 description 1
- 230000005014 ectopic expression Effects 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 210000002308 embryonic cell Anatomy 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000000105 enteric nervous system Anatomy 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethyl mercaptane Natural products CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 230000003328 fibroblastic effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 101150082979 gdnf gene Proteins 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 238000010363 gene targeting Methods 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 238000009650 gentamicin protection assay Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 230000000848 glutamatergic effect Effects 0.000 description 1
- 239000011544 gradient gel Substances 0.000 description 1
- 101150098203 grb2 gene Proteins 0.000 description 1
- 239000005090 green fluorescent protein Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 239000000710 homodimer Substances 0.000 description 1
- 102000047217 human NR4A3 Human genes 0.000 description 1
- 210000005104 human peripheral blood lymphocyte Anatomy 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 238000012744 immunostaining Methods 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 230000030214 innervation Effects 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 230000006662 intracellular pathway Effects 0.000 description 1
- 108091005979 iodinated proteins Proteins 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 210000000244 kidney pelvis Anatomy 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- 210000002332 leydig cell Anatomy 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 210000003750 lower gastrointestinal tract Anatomy 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000012092 media component Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 208000023356 medullary thyroid gland carcinoma Diseases 0.000 description 1
- 208000004840 megacolon Diseases 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 230000001617 migratory effect Effects 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 238000000329 molecular dynamics simulation Methods 0.000 description 1
- 230000001730 monoaminergic effect Effects 0.000 description 1
- 238000004264 monolayer culture Methods 0.000 description 1
- 230000001095 motoneuron effect Effects 0.000 description 1
- 239000012120 mounting media Substances 0.000 description 1
- 229940126619 mouse monoclonal antibody Drugs 0.000 description 1
- 210000001167 myeloblast Anatomy 0.000 description 1
- 210000003249 myenteric plexus Anatomy 0.000 description 1
- 230000032405 negative regulation of neuron apoptotic process Effects 0.000 description 1
- 230000002988 nephrogenic effect Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000000933 neural crest Anatomy 0.000 description 1
- 210000001982 neural crest cell Anatomy 0.000 description 1
- 210000000276 neural tube Anatomy 0.000 description 1
- 210000002241 neurite Anatomy 0.000 description 1
- 208000029986 neuroepithelioma Diseases 0.000 description 1
- 230000004766 neurogenesis Effects 0.000 description 1
- 230000016273 neuron death Effects 0.000 description 1
- 230000009207 neuronal maturation Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 238000006384 oligomerization reaction Methods 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 230000001582 osteoblastic effect Effects 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 238000004091 panning Methods 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000004031 partial agonist Substances 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 229950000964 pepstatin Drugs 0.000 description 1
- 108010091212 pepstatin Proteins 0.000 description 1
- FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 210000002856 peripheral neuron Anatomy 0.000 description 1
- 210000005047 peripherin Anatomy 0.000 description 1
- 210000003200 peritoneal cavity Anatomy 0.000 description 1
- 102000013415 peroxidase activity proteins Human genes 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 230000009120 phenotypic response Effects 0.000 description 1
- INAAIJLSXJJHOZ-UHFFFAOYSA-N pibenzimol Chemical compound C1CN(C)CCN1C1=CC=C(N=C(N2)C=3C=C4NC(=NC4=CC=3)C=3C=CC(O)=CC=3)C2=C1 INAAIJLSXJJHOZ-UHFFFAOYSA-N 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 108010055896 polyornithine Proteins 0.000 description 1
- 229920002714 polyornithine Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 238000010149 post-hoc-test Methods 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 230000007542 postnatal development Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 210000002250 primary motor neuron Anatomy 0.000 description 1
- 210000002243 primary neuron Anatomy 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 210000001202 rhombencephalon Anatomy 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000007423 screening assay Methods 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 210000001044 sensory neuron Anatomy 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 230000007781 signaling event Effects 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 230000022379 skeletal muscle tissue development Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 210000001032 spinal nerve Anatomy 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- QTENRWWVYAAPBI-YCRXJPFRSA-N streptomycin sulfate Chemical compound OS(O)(=O)=O.OS(O)(=O)=O.OS(O)(=O)=O.CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](N=C(N)N)[C@H](O)[C@@H](N=C(N)N)[C@H](O)[C@H]1O.CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](N=C(N)N)[C@H](O)[C@@H](N=C(N)N)[C@H](O)[C@H]1O QTENRWWVYAAPBI-YCRXJPFRSA-N 0.000 description 1
- TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical compound [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 210000002222 superior cervical ganglion Anatomy 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000013595 supernatant sample Substances 0.000 description 1
- 210000000331 sympathetic ganglia Anatomy 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 210000001103 thalamus Anatomy 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 208000013818 thyroid gland medullary carcinoma Diseases 0.000 description 1
- 229960001479 tosylchloramide sodium Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 239000012581 transferrin Substances 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 238000003146 transient transfection Methods 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- 102000027257 transmembrane receptors Human genes 0.000 description 1
- 108091008578 transmembrane receptors Proteins 0.000 description 1
- 210000003901 trigeminal nerve Anatomy 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 102000015533 trkA Receptor Human genes 0.000 description 1
- 108010064884 trkA Receptor Proteins 0.000 description 1
- 101150025395 trkA gene Proteins 0.000 description 1
- 101150113435 trkA1 gene Proteins 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 235000008979 vitamin B4 Nutrition 0.000 description 1
- 239000011579 vitamin B4 Substances 0.000 description 1
- 239000012130 whole-cell lysate Substances 0.000 description 1
- 238000001086 yeast two-hybrid system Methods 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/71—Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Physical Education & Sports Medicine (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Cell Biology (AREA)
- Epidemiology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Récepteurs du facteur neurotrophique dérivé de lignes de cellules gliales (GDNF), leur expression cellulaire, leur isolation, leur caractérisation biochimique et leurs séquences. L'invention concerne c-RET en tant qu'un récepteur de GDNF, ainsi que de nouveaux récepteurs supplémentaires. Elle concerne également la préparation d'anticorps monoclonaux dirigés contre GDNF.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/861,990 US6696259B1 (en) | 1995-11-13 | 1997-05-22 | Assays using glial cell line-derived neurotrophic factor receptors |
| US08/861,990 | 1997-05-22 | ||
| PCT/US1998/009056 WO1998052591A1 (fr) | 1997-05-22 | 1998-05-04 | Recepteurs du facteur neurotrophique derive de lignes de cellules gliales |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2290426A1 true CA2290426A1 (fr) | 1998-11-26 |
Family
ID=25337323
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002290426A Abandoned CA2290426A1 (fr) | 1997-05-22 | 1998-05-04 | Recepteurs du facteur neurotrophique derive de lignes de cellules gliales |
Country Status (8)
| Country | Link |
|---|---|
| EP (1) | EP1007072A4 (fr) |
| JP (1) | JP2001527418A (fr) |
| KR (1) | KR20010012826A (fr) |
| AU (1) | AU741208B2 (fr) |
| CA (1) | CA2290426A1 (fr) |
| NO (1) | NO995691L (fr) |
| NZ (1) | NZ501199A (fr) |
| WO (1) | WO1998052591A1 (fr) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6677135B1 (en) | 1996-05-08 | 2004-01-13 | Biogen, Inc. | Ret ligand (RetL) for stimulating neutral and renal growth |
| DE19816186A1 (de) * | 1998-04-14 | 1999-10-21 | Univ Muenchen L Maximilians | GDNF-kodierende DNA, Teile davon und GDNF-Varianten |
| FI20030130A0 (fi) | 2003-01-29 | 2003-01-29 | Licentia Oy | Seulontamenetelmä |
| IL261666B1 (en) | 2016-03-31 | 2024-05-01 | Ngm Biopharmaceuticals Inc | Related proteins and methods of using them |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR9710665A (pt) * | 1996-05-08 | 1999-08-17 | Biogen Inc | Compostos que promovem o desenvolvimento do tecido |
| DK1007666T3 (da) * | 1997-02-18 | 2006-05-08 | Genentech Inc | Neurturinreceptor |
| CA2291705A1 (fr) * | 1997-04-17 | 1998-10-22 | Washington University | Recepteurs des facteurs neurotrophiques associes au tgf-.beta. |
| WO1998053069A2 (fr) * | 1997-05-20 | 1998-11-26 | Human Genome Sciences, Inc. | Recepteurs du gdnf |
| EP0983354A2 (fr) * | 1997-05-30 | 2000-03-08 | Amgen Inc. | Recepteurs du facteur neurotrope |
-
1998
- 1998-05-04 KR KR19997010790A patent/KR20010012826A/ko not_active Application Discontinuation
- 1998-05-04 JP JP55040098A patent/JP2001527418A/ja not_active Ceased
- 1998-05-04 EP EP98920199A patent/EP1007072A4/fr not_active Withdrawn
- 1998-05-04 WO PCT/US1998/009056 patent/WO1998052591A1/fr not_active Application Discontinuation
- 1998-05-04 AU AU72825/98A patent/AU741208B2/en not_active Ceased
- 1998-05-04 NZ NZ501199A patent/NZ501199A/en unknown
- 1998-05-04 CA CA002290426A patent/CA2290426A1/fr not_active Abandoned
-
1999
- 1999-11-19 NO NO995691A patent/NO995691L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| JP2001527418A (ja) | 2001-12-25 |
| AU741208B2 (en) | 2001-11-22 |
| WO1998052591A1 (fr) | 1998-11-26 |
| EP1007072A4 (fr) | 2002-06-26 |
| NO995691D0 (no) | 1999-11-19 |
| EP1007072A1 (fr) | 2000-06-14 |
| AU7282598A (en) | 1998-12-11 |
| NO995691L (no) | 2000-01-19 |
| NZ501199A (en) | 2001-12-21 |
| KR20010012826A (ko) | 2001-02-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Trupp et al. | Multiple GPI-anchored receptors control GDNF-dependent and independent activation of the c-Ret receptor tyrosine kinase | |
| CA2409996C (fr) | Molecules d'acide nucleique et polypeptides nrg-2, et methodes diagnostiques et therapeutiques associees | |
| Lin et al. | Expression cloning of the TGF-β type II receptor, a functional transmembrane serine/threonine kinase | |
| Iwahara et al. | Molecular characterization of ALK, a receptor tyrosine kinase expressed specifically in the nervous system | |
| CA2063431C (fr) | Recepteurs de facteurs de croisance fibroblastes | |
| Tsuchida et al. | Molecular cloning of a novel type I receptor serine/threonine kinase for the TGFβ superfamily from rat brain | |
| US6379925B1 (en) | Angiogenic modulation by notch signal transduction | |
| JPH10510718A (ja) | 血管内皮増殖因子−ｂ | |
| JP2007167072A (ja) | 組換え血管内皮細胞増殖因子ｄ（ｖｅｇｆ−ｄ） | |
| AU2001274947A1 (en) | NRG-2 nucleic acid molecules, polypeptides, and diagnostic and therapeutic methods | |
| JPH09510612A (ja) | ヒトｔｒｋ受容体および神経栄養因子インヒビター | |
| CA2539918A1 (fr) | Produits vegf-c ou vegf-d et methodes de stimulation des cellules souches neurales | |
| WO1998057621A1 (fr) | Modulation angiogenique par transduction du signal de notch | |
| JP2008520222A (ja) | 変異ネトリン４、その断片及びこれらの薬剤としての使用 | |
| JPH025865A (ja) | ヒトの血小板由来の成長因子受容体 | |
| JP2002506627A (ja) | ９５個のヒト分泌タンパク質 | |
| Wennström et al. | cDNA cloning and expression of a human FGF receptor which binds acidic and basic FGF | |
| JP2000514777A (ja) | 骨形成タンパク質（ｏｐ−１）およびそのアナログの細胞表面レセプターａｌｋ−１およびそのアナログへの結合 | |
| US6696259B1 (en) | Assays using glial cell line-derived neurotrophic factor receptors | |
| AU718979B2 (en) | Glial cell line-derived neurotrophic factor receptors | |
| AU741208B2 (en) | Glial cell line-derived neurotrophic factor receptors | |
| JP2011115169A (ja) | Ｋｃｎｂ：新規なカリウムチャネルタンパク質 | |
| JP2003510029A (ja) | Ｅｇｆｈ２遺伝子および遺伝子産物 | |
| MXPA98003767A (en) | Receivers of the neurotrophic factor derived from cell line gl | |
| MXPA99010773A (en) | Glial cell line-derived neurotrophic factor receptors |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Dead |