JP2006506994A - リン酸化ndrキナーゼ - Google Patents
リン酸化ndrキナーゼ Download PDFInfo
- Publication number
- JP2006506994A JP2006506994A JP2004554468A JP2004554468A JP2006506994A JP 2006506994 A JP2006506994 A JP 2006506994A JP 2004554468 A JP2004554468 A JP 2004554468A JP 2004554468 A JP2004554468 A JP 2004554468A JP 2006506994 A JP2006506994 A JP 2006506994A
- Authority
- JP
- Japan
- Prior art keywords
- ndr
- polypeptide
- amino acid
- kinase
- ndr1
- 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.)
- Pending
Links
- 101000701401 Homo sapiens Serine/threonine-protein kinase 38 Proteins 0.000 title description 128
- 108091000080 Phosphotransferase Proteins 0.000 claims abstract description 127
- 102000020233 phosphotransferase Human genes 0.000 claims abstract description 127
- 238000000034 method Methods 0.000 claims abstract description 45
- 238000012216 screening Methods 0.000 claims abstract description 19
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 122
- 230000000694 effects Effects 0.000 claims description 101
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 92
- 229920001184 polypeptide Polymers 0.000 claims description 72
- 238000006366 phosphorylation reaction Methods 0.000 claims description 67
- 230000026731 phosphorylation Effects 0.000 claims description 66
- 150000001413 amino acids Chemical class 0.000 claims description 55
- QNDVLZJODHBUFM-WFXQOWMNSA-N okadaic acid Chemical compound C([C@H](O1)[C@H](C)/C=C/[C@H]2CC[C@@]3(CC[C@H]4O[C@@H](C([C@@H](O)[C@@H]4O3)=C)[C@@H](O)C[C@H](C)[C@@H]3[C@@H](CC[C@@]4(OCCCC4)O3)C)O2)C(C)=C[C@]21O[C@H](C[C@@](C)(O)C(O)=O)CC[C@H]2O QNDVLZJODHBUFM-WFXQOWMNSA-N 0.000 claims description 54
- VEFJHAYOIAAXEU-UHFFFAOYSA-N okadaic acid Natural products CC(CC(O)C1OC2CCC3(CCC(O3)C=CC(C)C4CC(=CC5(OC(CC(C)(O)C(=O)O)CCC5O)O4)C)OC2C(O)C1C)C6OC7(CCCCO7)CCC6C VEFJHAYOIAAXEU-UHFFFAOYSA-N 0.000 claims description 54
- 108090000623 proteins and genes Proteins 0.000 claims description 47
- 102000004169 proteins and genes Human genes 0.000 claims description 39
- 230000003993 interaction Effects 0.000 claims description 37
- 239000012634 fragment Substances 0.000 claims description 30
- 230000027455 binding Effects 0.000 claims description 29
- 239000000284 extract Substances 0.000 claims description 17
- 101710154408 Serine/threonine-protein kinase sax-1 Proteins 0.000 claims description 15
- 101710130108 Serine/threonine-protein kinase tricornered Proteins 0.000 claims description 15
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 13
- 125000000539 amino acid group Chemical group 0.000 claims description 12
- 230000002829 reductive effect Effects 0.000 claims description 10
- 101150032346 NDRG1 gene Proteins 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 101100133106 Mus musculus Ndrg2 gene Proteins 0.000 claims description 8
- 230000002378 acidificating effect Effects 0.000 claims description 8
- 230000008859 change Effects 0.000 claims description 8
- 230000019491 signal transduction Effects 0.000 claims description 8
- 230000005856 abnormality Effects 0.000 claims description 6
- 230000004663 cell proliferation Effects 0.000 claims description 5
- 239000000556 agonist Substances 0.000 claims description 4
- 239000005557 antagonist Substances 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 102000039446 nucleic acids Human genes 0.000 claims description 4
- 108020004707 nucleic acids Proteins 0.000 claims description 4
- 150000007523 nucleic acids Chemical class 0.000 claims description 4
- 239000000356 contaminant Substances 0.000 claims description 3
- 108090000144 Human Proteins Proteins 0.000 claims description 2
- 102000003839 Human Proteins Human genes 0.000 claims description 2
- 101000969581 Homo sapiens MOB kinase activator 1A Proteins 0.000 claims 5
- 102100021437 MOB kinase activator 1A Human genes 0.000 claims 5
- 238000004458 analytical method Methods 0.000 abstract description 23
- 101710199605 Endoribonuclease Proteins 0.000 abstract description 3
- 101710113029 Serine/threonine-protein kinase Proteins 0.000 abstract description 3
- 239000000463 material Substances 0.000 abstract description 3
- 102100030011 Endoribonuclease Human genes 0.000 abstract 1
- 102100030514 Serine/threonine-protein kinase 38 Human genes 0.000 description 126
- 101000979748 Homo sapiens Protein NDRG1 Proteins 0.000 description 79
- 210000004027 cell Anatomy 0.000 description 63
- 101000821885 Homo sapiens Protein S100-B Proteins 0.000 description 47
- 102100021487 Protein S100-B Human genes 0.000 description 46
- 235000001014 amino acid Nutrition 0.000 description 43
- 230000035578 autophosphorylation Effects 0.000 description 41
- 235000018102 proteins Nutrition 0.000 description 34
- 101001045553 Homo sapiens Hemogen Proteins 0.000 description 29
- 101000697608 Homo sapiens Serine/threonine-protein kinase 38-like Proteins 0.000 description 22
- 102100027898 Serine/threonine-protein kinase 38-like Human genes 0.000 description 21
- 150000001875 compounds Chemical class 0.000 description 19
- 230000035772 mutation Effects 0.000 description 19
- 230000001105 regulatory effect Effects 0.000 description 19
- 101100007328 Cocos nucifera COS-1 gene Proteins 0.000 description 18
- 230000001419 dependent effect Effects 0.000 description 18
- 238000000338 in vitro Methods 0.000 description 17
- 241000282414 Homo sapiens Species 0.000 description 15
- 102000001253 Protein Kinase Human genes 0.000 description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
- 230000004913 activation Effects 0.000 description 14
- 108060006633 protein kinase Proteins 0.000 description 14
- YJIYWYAMZFVECX-UHFFFAOYSA-N 2-[N-[2-(acetyloxymethoxy)-2-oxoethyl]-2-[2-[2-[bis[2-(acetyloxymethoxy)-2-oxoethyl]amino]phenoxy]ethoxy]anilino]acetic acid acetyloxymethyl ester Chemical compound CC(=O)OCOC(=O)CN(CC(=O)OCOC(C)=O)C1=CC=CC=C1OCCOC1=CC=CC=C1N(CC(=O)OCOC(C)=O)CC(=O)OCOC(C)=O YJIYWYAMZFVECX-UHFFFAOYSA-N 0.000 description 13
- 235000004279 alanine Nutrition 0.000 description 13
- 238000001727 in vivo Methods 0.000 description 13
- 238000011534 incubation Methods 0.000 description 11
- DHCLVCXQIBBOPH-UHFFFAOYSA-N Glycerol 2-phosphate Chemical compound OCC(CO)OP(O)(O)=O DHCLVCXQIBBOPH-UHFFFAOYSA-N 0.000 description 10
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 10
- 229920002684 Sepharose Polymers 0.000 description 10
- 239000002299 complementary DNA Substances 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- 239000000499 gel Substances 0.000 description 9
- 230000014509 gene expression Effects 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 230000000638 stimulation Effects 0.000 description 9
- 241000699666 Mus <mouse, genus> Species 0.000 description 8
- 238000007792 addition Methods 0.000 description 8
- 230000002209 hydrophobic effect Effects 0.000 description 8
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 8
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 8
- 239000013612 plasmid Substances 0.000 description 8
- 241000894007 species Species 0.000 description 8
- 239000004475 Arginine Substances 0.000 description 7
- 101100348617 Candida albicans (strain SC5314 / ATCC MYA-2876) NIK1 gene Proteins 0.000 description 7
- 229910019142 PO4 Inorganic materials 0.000 description 7
- 101100007329 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) COS1 gene Proteins 0.000 description 7
- 108090000631 Trypsin Proteins 0.000 description 7
- 102000004142 Trypsin Human genes 0.000 description 7
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 7
- 230000003197 catalytic effect Effects 0.000 description 7
- 239000010452 phosphate Substances 0.000 description 7
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 7
- 239000000758 substrate Substances 0.000 description 7
- 239000012588 trypsin Substances 0.000 description 7
- 238000011144 upstream manufacturing Methods 0.000 description 7
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 6
- 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 6
- 241000283973 Oryctolagus cuniculus Species 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 239000011324 bead Substances 0.000 description 6
- PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 description 6
- 239000011575 calcium Substances 0.000 description 6
- 230000007423 decrease Effects 0.000 description 6
- 150000002500 ions Chemical class 0.000 description 6
- 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 6
- 108010052968 leupeptin Proteins 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- 239000002773 nucleotide Substances 0.000 description 6
- 125000003729 nucleotide group Chemical group 0.000 description 6
- 101100532400 Bos taurus S100B gene Proteins 0.000 description 5
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 5
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 5
- 239000004472 Lysine Substances 0.000 description 5
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- 108010001441 Phosphopeptides Proteins 0.000 description 5
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 5
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 5
- 102220626054 Serine/threonine-protein kinase 38-like_T75A_mutation Human genes 0.000 description 5
- 102220513909 Serine/threonine-protein kinase 38_T74A_mutation Human genes 0.000 description 5
- HATRDXDCPOXQJX-UHFFFAOYSA-N Thapsigargin Natural products CCCCCCCC(=O)OC1C(OC(O)C(=C/C)C)C(=C2C3OC(=O)C(C)(O)C3(O)C(CC(C)(OC(=O)C)C12)OC(=O)CCC)C HATRDXDCPOXQJX-UHFFFAOYSA-N 0.000 description 5
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 5
- 239000004473 Threonine Substances 0.000 description 5
- 239000002738 chelating agent Substances 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 238000000749 co-immunoprecipitation Methods 0.000 description 5
- 108010073357 cyanoginosin LR Proteins 0.000 description 5
- 230000001086 cytosolic effect Effects 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 239000013604 expression vector Substances 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 239000012133 immunoprecipitate Substances 0.000 description 5
- 238000001114 immunoprecipitation Methods 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- ZYZCGGRZINLQBL-GWRQVWKTSA-N microcystin-LR Chemical compound C([C@H](OC)[C@@H](C)\C=C(/C)\C=C\[C@H]1[C@@H](C(=O)N[C@H](CCC(=O)N(C)C(=C)C(=O)N[C@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]([C@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1)C(O)=O)C(O)=O)C)C1=CC=CC=C1 ZYZCGGRZINLQBL-GWRQVWKTSA-N 0.000 description 5
- DIDLWIPCWUSYPF-UHFFFAOYSA-N microcystin-LR Natural products COC(Cc1ccccc1)C(C)C=C(/C)C=CC2NC(=O)C(NC(CCCNC(=N)N)C(=O)O)NC(=O)C(C)C(NC(=O)C(NC(CC(C)C)C(=O)O)NC(=O)C(C)NC(=O)C(=C)N(C)C(=O)CCC(NC(=O)C2C)C(=O)O)C(=O)O DIDLWIPCWUSYPF-UHFFFAOYSA-N 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 239000006228 supernatant Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 241000588724 Escherichia coli Species 0.000 description 4
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 4
- 229930186657 Lat Natural products 0.000 description 4
- 241000244206 Nematoda Species 0.000 description 4
- 108010002747 Pfu DNA polymerase Proteins 0.000 description 4
- 102100030919 Phosphatidylcholine:ceramide cholinephosphotransferase 1 Human genes 0.000 description 4
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 4
- 239000006180 TBST buffer Substances 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 4
- 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 4
- 229940088598 enzyme Drugs 0.000 description 4
- -1 for example Proteins 0.000 description 4
- 102000037865 fusion proteins Human genes 0.000 description 4
- 108020001507 fusion proteins Proteins 0.000 description 4
- 239000012742 immunoprecipitation (IP) buffer Substances 0.000 description 4
- 108020004999 messenger RNA Proteins 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 239000002953 phosphate buffered saline Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- IXFPJGBNCFXKPI-FSIHEZPISA-N thapsigargin Chemical compound CCCC(=O)O[C@H]1C[C@](C)(OC(C)=O)[C@H]2[C@H](OC(=O)CCCCCCC)[C@@H](OC(=O)C(\C)=C/C)C(C)=C2[C@@H]2OC(=O)[C@@](C)(O)[C@]21O IXFPJGBNCFXKPI-FSIHEZPISA-N 0.000 description 4
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- FTEDXVNDVHYDQW-UHFFFAOYSA-N BAPTA Chemical compound OC(=O)CN(CC(O)=O)C1=CC=CC=C1OCCOC1=CC=CC=C1N(CC(O)=O)CC(O)=O FTEDXVNDVHYDQW-UHFFFAOYSA-N 0.000 description 3
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 3
- 239000007995 HEPES buffer Substances 0.000 description 3
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 3
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 3
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 101100293885 Mus musculus Ndrg1 gene Proteins 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- 108010077850 Nuclear Localization Signals Proteins 0.000 description 3
- 108091005804 Peptidases Proteins 0.000 description 3
- 102000035195 Peptidases Human genes 0.000 description 3
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 3
- 108010023918 S100 Calcium Binding Protein beta Subunit Proteins 0.000 description 3
- 102000011425 S100 Calcium Binding Protein beta Subunit Human genes 0.000 description 3
- ZKHQWZAMYRWXGA-KNYAHOBESA-N [[(2r,3s,4r,5r)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] dihydroxyphosphoryl hydrogen phosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)O[32P](O)(O)=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KNYAHOBESA-N 0.000 description 3
- 239000012190 activator Substances 0.000 description 3
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 235000019253 formic acid Nutrition 0.000 description 3
- 230000004927 fusion Effects 0.000 description 3
- 235000013922 glutamic acid Nutrition 0.000 description 3
- 239000004220 glutamic acid Substances 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 3
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 3
- 239000003202 long acting thyroid stimulator Substances 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 3
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 3
- BZQFBWGGLXLEPQ-REOHCLBHSA-N phosphoserine Chemical group OC(=O)[C@@H](N)COP(O)(O)=O BZQFBWGGLXLEPQ-REOHCLBHSA-N 0.000 description 3
- 238000002541 precursor ion scan Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000012163 sequencing technique Methods 0.000 description 3
- 150000003384 small molecules Chemical class 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 238000010183 spectrum analysis Methods 0.000 description 3
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 3
- 239000013598 vector Substances 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- QFVHZQCOUORWEI-UHFFFAOYSA-N 4-[(4-anilino-5-sulfonaphthalen-1-yl)diazenyl]-5-hydroxynaphthalene-2,7-disulfonic acid Chemical compound C=12C(O)=CC(S(O)(=O)=O)=CC2=CC(S(O)(=O)=O)=CC=1N=NC(C1=CC=CC(=C11)S(O)(=O)=O)=CC=C1NC1=CC=CC=C1 QFVHZQCOUORWEI-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 101000936911 Chionoecetes opilio Sarcoplasmic/endoplasmic reticulum calcium ATPase Proteins 0.000 description 2
- 108090000317 Chymotrypsin Proteins 0.000 description 2
- 241000255601 Drosophila melanogaster Species 0.000 description 2
- 102100030013 Endoribonuclease Human genes 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- HVLSXIKZNLPZJJ-TXZCQADKSA-N HA peptide Chemical compound C([C@@H](C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 HVLSXIKZNLPZJJ-TXZCQADKSA-N 0.000 description 2
- 101100258047 Homo sapiens STK38 gene Proteins 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 101100258048 Mus musculus Stk38 gene Proteins 0.000 description 2
- 101100422517 Mus musculus Stk38l gene Proteins 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 101100384865 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) cot-1 gene Proteins 0.000 description 2
- BZQFBWGGLXLEPQ-UHFFFAOYSA-N O-phosphoryl-L-serine Natural products OC(=O)C(N)COP(O)(O)=O BZQFBWGGLXLEPQ-UHFFFAOYSA-N 0.000 description 2
- 239000002033 PVDF binder Substances 0.000 description 2
- 101800004191 Peptide P2 Proteins 0.000 description 2
- 102000045595 Phosphoprotein Phosphatases Human genes 0.000 description 2
- 108700019535 Phosphoprotein Phosphatases Proteins 0.000 description 2
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 101150015535 SAX1 gene Proteins 0.000 description 2
- 241000235347 Schizosaccharomyces pombe Species 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- 101710171512 Serine/threonine-protein kinase 38-like Proteins 0.000 description 2
- 101710120037 Toxin CcdB Proteins 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 238000010306 acid treatment Methods 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 239000008186 active pharmaceutical agent Substances 0.000 description 2
- 238000001042 affinity chromatography Methods 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229960002376 chymotrypsin Drugs 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 2
- 230000009089 cytolysis Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 239000003599 detergent Substances 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 229950006137 dexfosfoserine Drugs 0.000 description 2
- 239000007850 fluorescent dye Substances 0.000 description 2
- 229930195712 glutamate Natural products 0.000 description 2
- 239000000710 homodimer Substances 0.000 description 2
- 102000052545 human STK38L Human genes 0.000 description 2
- 208000026278 immune system disease Diseases 0.000 description 2
- 238000003119 immunoblot Methods 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 230000000415 inactivating effect Effects 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 2
- 239000006166 lysate Substances 0.000 description 2
- 238000013507 mapping Methods 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- USRGIUJOYOXOQJ-GBXIJSLDSA-N phosphothreonine Chemical group OP(=O)(O)O[C@H](C)[C@H](N)C(O)=O USRGIUJOYOXOQJ-GBXIJSLDSA-N 0.000 description 2
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 235000019833 protease Nutrition 0.000 description 2
- 230000009822 protein phosphorylation Effects 0.000 description 2
- 230000002285 radioactive effect Effects 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 230000022983 regulation of cell cycle Effects 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound 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](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000004885 tandem mass spectrometry Methods 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 108020003589 5' Untranslated Regions Proteins 0.000 description 1
- 108091006112 ATPases Proteins 0.000 description 1
- 102000057290 Adenosine Triphosphatases Human genes 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- JQFZHHSQMKZLRU-IUCAKERBSA-N Arg-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](N)CCCN=C(N)N JQFZHHSQMKZLRU-IUCAKERBSA-N 0.000 description 1
- OMSMPWHEGLNQOD-UWVGGRQHSA-N Asn-Phe Chemical compound NC(=O)C[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 OMSMPWHEGLNQOD-UWVGGRQHSA-N 0.000 description 1
- 102100026189 Beta-galactosidase Human genes 0.000 description 1
- 102100025248 C-X-C motif chemokine 10 Human genes 0.000 description 1
- 101150008950 CBK1 gene Proteins 0.000 description 1
- 101150012716 CDK1 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 102000005701 Calcium-Binding Proteins Human genes 0.000 description 1
- 108010045403 Calcium-Binding Proteins Proteins 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 101100326161 Chlamydomonas reinhardtii BKT gene Proteins 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 241000186031 Corynebacteriaceae Species 0.000 description 1
- 238000001712 DNA sequencing Methods 0.000 description 1
- 101001031598 Dictyostelium discoideum Probable serine/threonine-protein kinase fhkC Proteins 0.000 description 1
- 108010000518 Dual-Specificity Phosphatases Proteins 0.000 description 1
- 108030004793 Dual-specificity kinases Proteins 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 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 1
- 241000283074 Equus asinus Species 0.000 description 1
- 108090000371 Esterases Proteins 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 108010014173 Factor X Proteins 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- WOACHWLUOFZLGJ-GUBZILKMSA-N Gln-Arg-Gln Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(O)=O WOACHWLUOFZLGJ-GUBZILKMSA-N 0.000 description 1
- 108010051815 Glutamyl endopeptidase Proteins 0.000 description 1
- 108010070675 Glutathione transferase Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 241001622557 Hesperia Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000858088 Homo sapiens C-X-C motif chemokine 10 Proteins 0.000 description 1
- 101001030211 Homo sapiens Myc proto-oncogene protein Proteins 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 125000003440 L-leucyl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])C(C([H])([H])[H])([H])C([H])([H])[H] 0.000 description 1
- 125000003798 L-tyrosyl group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C([H])([H])C1=C([H])C([H])=C(O[H])C([H])=C1[H] 0.000 description 1
- 125000003580 L-valyl group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(C([H])([H])[H])(C([H])([H])[H])[H] 0.000 description 1
- LCPYQJIKPJDLLB-UWVGGRQHSA-N Leu-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@H](C(O)=O)CC(C)C LCPYQJIKPJDLLB-UWVGGRQHSA-N 0.000 description 1
- WYEXWKAWMNJKPN-UBHSHLNASA-N Met-Ala-Phe Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)NC(=O)[C@H](CCSC)N WYEXWKAWMNJKPN-UBHSHLNASA-N 0.000 description 1
- 102000005431 Molecular Chaperones Human genes 0.000 description 1
- 108010006519 Molecular Chaperones Proteins 0.000 description 1
- 108700025784 N-myc downstream-regulated gene 1 Proteins 0.000 description 1
- 206010061309 Neoplasm progression Diseases 0.000 description 1
- 241000221961 Neurospora crassa Species 0.000 description 1
- 208000012868 Overgrowth 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
- 101800004196 Peptide P4 Proteins 0.000 description 1
- JXWLMUIXUXLIJR-QWRGUYRKSA-N Phe-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CC=CC=C1 JXWLMUIXUXLIJR-QWRGUYRKSA-N 0.000 description 1
- 102000007982 Phosphoproteins Human genes 0.000 description 1
- 108010089430 Phosphoproteins Proteins 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 108010058956 Protein Phosphatase 2 Proteins 0.000 description 1
- 102000006478 Protein Phosphatase 2 Human genes 0.000 description 1
- 229940122454 Protein phosphatase 2A inhibitor Drugs 0.000 description 1
- 108700020978 Proto-Oncogene Proteins 0.000 description 1
- 102000052575 Proto-Oncogene Human genes 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 101100222379 Rattus norvegicus Cxcl10 gene Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 108091081024 Start codon Proteins 0.000 description 1
- NYQIZWROIMIQSL-VEVYYDQMSA-N Thr-Pro-Asn Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C(O)=O NYQIZWROIMIQSL-VEVYYDQMSA-N 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 108700025716 Tumor Suppressor Genes Proteins 0.000 description 1
- 102000044209 Tumor Suppressor Genes Human genes 0.000 description 1
- 108010040002 Tumor Suppressor Proteins Proteins 0.000 description 1
- 102000001742 Tumor Suppressor Proteins Human genes 0.000 description 1
- AOLHUMAVONBBEZ-STQMWFEESA-N Tyr-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 AOLHUMAVONBBEZ-STQMWFEESA-N 0.000 description 1
- 244000301083 Ustilago maydis Species 0.000 description 1
- 101100053619 Yersinia enterocolitica yscF gene Proteins 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000006229 amino acid addition Effects 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 108010062796 arginyllysine Proteins 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000001908 autoinhibitory effect Effects 0.000 description 1
- 108010058966 bacteriophage T7 induced DNA polymerase Proteins 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 102000021115 calcium ion binding proteins Human genes 0.000 description 1
- 108091011132 calcium ion binding proteins Proteins 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000012761 co-transfection Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 238000002101 electrospray ionisation tandem mass spectrometry Methods 0.000 description 1
- 238000001976 enzyme digestion Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 238000003804 extraction from natural source Methods 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 102000034356 gene-regulatory proteins Human genes 0.000 description 1
- 108091006104 gene-regulatory proteins Proteins 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000012145 high-salt buffer Substances 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 108091008039 hormone receptors Proteins 0.000 description 1
- 102000046438 human CXCL10 Human genes 0.000 description 1
- 102000057348 human HEMGN Human genes 0.000 description 1
- 102000053563 human MYC Human genes 0.000 description 1
- 102000057388 human S100B Human genes 0.000 description 1
- 102000054800 human STK38 Human genes 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 238000012744 immunostaining Methods 0.000 description 1
- 230000003308 immunostimulating effect Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000031146 intracellular signal transduction Effects 0.000 description 1
- 230000004068 intracellular signaling Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- PGLTVOMIXTUURA-UHFFFAOYSA-N iodoacetamide Chemical compound NC(=O)CI PGLTVOMIXTUURA-UHFFFAOYSA-N 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 108010091798 leucylleucine Proteins 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000003712 lysosome Anatomy 0.000 description 1
- 230000001868 lysosomic effect Effects 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 230000011278 mitosis Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 238000000329 molecular dynamics simulation Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 230000000869 mutational effect Effects 0.000 description 1
- 210000004897 n-terminal region Anatomy 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229940080469 phosphocellulose Drugs 0.000 description 1
- ZLKNTGQAQQSIFV-HQAKDUOCSA-N pkip Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O)[C@@H](C)O)[C@@H](C)CC)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@@H](NC(=O)[C@@H](N)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 ZLKNTGQAQQSIFV-HQAKDUOCSA-N 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229940124606 potential therapeutic agent Drugs 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 235000019419 proteases Nutrition 0.000 description 1
- 238000000164 protein isolation Methods 0.000 description 1
- 108010086868 protein kinase inhibitor peptide Proteins 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000031539 regulation of cell division Effects 0.000 description 1
- 230000025053 regulation of cell proliferation Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 210000003660 reticulum Anatomy 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 239000012723 sample buffer Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229930009674 sesquiterpene lactone Natural products 0.000 description 1
- 150000002107 sesquiterpene lactone derivatives Chemical class 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 210000002536 stromal cell Anatomy 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000005758 transcription activity Effects 0.000 description 1
- 239000012096 transfection reagent Substances 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000005740 tumor formation Effects 0.000 description 1
- 230000005751 tumor progression Effects 0.000 description 1
- 150000003668 tyrosines Chemical class 0.000 description 1
- 108010051110 tyrosyl-lysine Proteins 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000001086 yeast two-hybrid system Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/10—Transferases (2.)
- C12N9/12—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
- C12N9/1205—Phosphotransferases with an alcohol group as acceptor (2.7.1), e.g. protein kinases
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- 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)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Wood Science & Technology (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- General Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Enzymes And Modification Thereof (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0227562.6A GB0227562D0 (en) | 2002-11-26 | 2002-11-26 | Phorphorylated NDR Kinase |
| PCT/EP2003/013251 WO2004048576A1 (en) | 2002-11-26 | 2003-11-25 | Phosphorylated ndr kinase |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010160462A Division JP2010279371A (ja) | 2002-11-26 | 2010-07-15 | リン酸化ndrキナーゼ |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2006506994A true JP2006506994A (ja) | 2006-03-02 |
| JP2006506994A5 JP2006506994A5 (https=) | 2010-09-09 |
Family
ID=9948532
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2004554468A Pending JP2006506994A (ja) | 2002-11-26 | 2003-11-25 | リン酸化ndrキナーゼ |
| JP2010160462A Withdrawn JP2010279371A (ja) | 2002-11-26 | 2010-07-15 | リン酸化ndrキナーゼ |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010160462A Withdrawn JP2010279371A (ja) | 2002-11-26 | 2010-07-15 | リン酸化ndrキナーゼ |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US8008452B2 (https=) |
| EP (1) | EP1567646A1 (https=) |
| JP (2) | JP2006506994A (https=) |
| AU (1) | AU2003286181A1 (https=) |
| GB (1) | GB0227562D0 (https=) |
| WO (1) | WO2004048576A1 (https=) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8642569B2 (en) | 2009-01-21 | 2014-02-04 | The General Hospital Corporation | Methods for expansion of hematopoietic stem and progenitor cells |
| US20230193267A1 (en) * | 2021-10-19 | 2023-06-22 | Animatus Biosciences, Inc. | Cardiac cell proliferation by administering inhibitors of sav1, nf2, mob1 and/or mutant srf |
| CN119497621A (zh) | 2022-06-20 | 2025-02-21 | 杏林制药株式会社 | 纤维化疾病治疗用医药组合物 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU4388296A (en) | 1994-12-22 | 1996-07-10 | Novartis Ag | Nuclear protein serine/threonine kinases |
| PT862622E (pt) | 1995-11-16 | 2005-01-31 | Novartis Ag | Metodo de rastreio para compostos que interagem com proteina cinase rac |
| GB9921121D0 (en) | 1999-09-07 | 1999-11-10 | Novartis Ag | Organic compounds |
-
2002
- 2002-11-26 GB GBGB0227562.6A patent/GB0227562D0/en not_active Ceased
-
2003
- 2003-11-25 EP EP03776917A patent/EP1567646A1/en not_active Withdrawn
- 2003-11-25 US US10/535,920 patent/US8008452B2/en not_active Expired - Lifetime
- 2003-11-25 WO PCT/EP2003/013251 patent/WO2004048576A1/en not_active Ceased
- 2003-11-25 AU AU2003286181A patent/AU2003286181A1/en not_active Abandoned
- 2003-11-25 JP JP2004554468A patent/JP2006506994A/ja active Pending
-
2010
- 2010-07-15 JP JP2010160462A patent/JP2010279371A/ja not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| GB0227562D0 (en) | 2002-12-31 |
| WO2004048576A1 (en) | 2004-06-10 |
| AU2003286181A1 (en) | 2004-06-18 |
| US8008452B2 (en) | 2011-08-30 |
| US20060172374A1 (en) | 2006-08-03 |
| JP2010279371A (ja) | 2010-12-16 |
| EP1567646A1 (en) | 2005-08-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Wang et al. | Eukaryotic initiation factor 2B: identification of multiple phosphorylation sites in the ϵ‐subunit and their functions in vivo | |
| Tang et al. | Two distinct mechanisms for negative regulation of the Wee1 protein kinase. | |
| Brunet et al. | 14-3-3 transits to the nucleus and participates in dynamic nucleocytoplasmic transport | |
| Chen et al. | The casein kinase II β subunit binds to Mos and inhibits Mos activity | |
| Vitari et al. | WNK1, the kinase mutated in an inherited high-blood-pressure syndrome, is a novel PKB (protein kinase B)/Akt substrate | |
| Watanabe et al. | Regulation of the human WEE1Hu CDK tyrosine 15‐kinase during the cell cycle. | |
| Kollewe et al. | Sequential autophosphorylation steps in the interleukin-1 receptor-associated kinase-1 regulate its availability as an adapter in interleukin-1 signaling | |
| Scholz et al. | Autoactivation of transforming growth factor β-activated kinase 1 is a sequential bimolecular process | |
| Donella-Deana et al. | Tyrosine phosphorylation of protein kinase CK2 by Src-related tyrosine kinases correlates with increased catalytic activity | |
| Kirchhefer et al. | Protein phosphatase 2A is regulated by protein kinase Cα (PKCα)-dependent phosphorylation of its targeting subunit B56α at Ser41 | |
| Yamashita et al. | Molecular mechanisms of the activation of maturation-promoting factor during goldfish oocyte maturation | |
| Kuma et al. | Identification of glycogen synthase as a new substrate for stress-activated protein kinase 2b/p38beta | |
| Oe et al. | Cytoplasmic occurrence of the Chk1/Cdc25 pathway and regulation of Chk1 in Xenopus oocytes | |
| JP2000502097A (ja) | タンパク質合成の制御、および作用薬のスクリーニング法 | |
| JP2008115164A (ja) | IκBキナーゼ、そのサブユニット、およびこれらを使用する方法 | |
| Nagy et al. | Activation of AtMPK9 through autophosphorylation that makes it independent of the canonical MAPK cascades. | |
| Wolff et al. | Interaction of casein kinase 1 delta (CK1δ) with the light chain LC2 of microtubule associated protein 1A (MAP1A) | |
| US20070196883A1 (en) | Enzyme | |
| AU726294B2 (en) | Ikk-alpha proteins, nucleic acids and methods | |
| King et al. | The adaptor protein Grb14 regulates the localization of 3-phosphoinositide-dependent kinase-1 | |
| Phin et al. | Mutational analysis of ribosomal S6 kinase 2 shows differential regulation of its kinase activity from that of ribosomal S6 kinase 1 | |
| MURÁNYI et al. | Identification and localization of myosin phosphatase in human platelets | |
| WO2000019205A1 (en) | Inhibition of pak activation of raf-1 | |
| JP2010279371A (ja) | リン酸化ndrキナーゼ | |
| Kurioka et al. | Molecular cloning and characterization of a novel protein serine/threonine kinase highly expressed in mouse embryo |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20061025 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20061025 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20090811 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20091111 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20091118 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20091211 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20091218 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100112 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20100316 |
|
| A524 | Written submission of copy of amendment under article 19 pct |
Free format text: JAPANESE INTERMEDIATE CODE: A524 Effective date: 20100715 |
|
| A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20100906 |
|
| A912 | Re-examination (zenchi) completed and case transferred to appeal board |
Free format text: JAPANESE INTERMEDIATE CODE: A912 Effective date: 20101105 |