Rac1 (RAS-related C3 botulinus toxin substrate 1) は、ヒト細胞に存在するタンパク質であり、RAC1遺伝子によりコードされている[5][6]。RAC1は選択的スプライシングにより異なる機能を持ったいくつかのタンパク質を生成しており、このうちの1つがRac1である[7]。
RAC1 | |||||||||||||||||
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識別子 | |||||||||||||||||
記号 | RAC1, MIG5, Rac-1, TC-25, p21-Rac1, ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1), Rac family small GTPase 1, MRD48 | ||||||||||||||||
外部ID | OMIM: 602048 MGI: 97845 HomoloGene: 69035 GeneCards: RAC1 | ||||||||||||||||
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オルソログ | |||||||||||||||||
種 | ヒト | マウス | |||||||||||||||
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Ensembl |
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UniProt |
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RefSeq (mRNA) |
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RefSeq (タンパク質) |
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場所 (UCSC) | Chr 7: 6.37 – 6.4 Mb | Chr 7: 143.49 – 143.51 Mb | |||||||||||||||
PubMed検索 | [3] | [4] | |||||||||||||||
ウィキデータ | |||||||||||||||||
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Rac1は、悪性黒色腫[8][9][10]や肺非小細胞癌[11] を含むさまざまな癌の発生において、重要な役割を果たしていると考えられている。そのため、現在これらの疾患に対する治療標的と考えられている[12]。
機能
低分子量GTPアーゼの1つであるうえ、RhoファミリーGタンパク質であるRacサブファミリーのメンバーでもある。このスーパーファミリーのメンバーは、細胞の増殖や細胞骨格の再構築、プロテインキナーゼの活性化などさまざまな細胞における事象を制御している[13]。
Rac1は、細胞周期や細胞接着、(アクチンネットワークを介した)細胞運動、上皮細胞における(悪性形質転換)(上皮幹細胞維持における必要物質であると考えられている)などを含む多くの細胞プロセスにおける、多方面的な制御因子である。
相互作用
(ARFIP2)[14][15][16]、(Myotonic dystrophy protein kinase)[17]、(T-cell lymphoma invasion and metastasis-inducing protein 1)[18][19]、(PARD6B)[20]、PAK1[21][22][23]、(PAK3)[14]、(ARHGDIA)[24][25][26][27][28][29]、(Myd88)[30]、(PARD6A),[20][31]、STAT3[32]、(IQGAP2)[33]、(NCKAP1)[34]、(IQGAP1)[23][35][36][37]、(FHOD1)[38]、(BAIAP2)[39]、(RICS)[40][41]、(FMNL1)[42]などのタンパク質と相互作用することが明らかにされている。
脚注
- ^ a b c GRCh38: Ensembl release 89: ENSG00000136238 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000001847 - Ensembl, May 2017
- ^ Human PubMed Reference:
- ^ Mouse PubMed Reference:
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- ^ Jordan P, Brazåo R, Boavida MG, Gespach C, Chastre E (November 1999). “Cloning of a novel human Rac1b splice variant with increased expression in colorectal tumors”. Oncogene 18 (48): 6835–9. doi:10.1038/sj.onc.1203233. PMID (10597294).
- ^ Zhou, C; Licciulli, S; Avila, J L; Cho, M; Troutman, S; Jiang, P; Kossenkov, A V; Showe, L C et al. (2012). “The Rac1 splice form Rac1b promotes K-ras-induced lung tumorigenesis”. Oncogene. doi:10.1038/onc.2012.99. ISSN 0950-9232.
- ^ Hodis, E; Watson, IR; Kryukov, GV; Arold, ST; Imielinski, M; Theurillat, JP; Nickerson, E; Auclair, D; Li, L; Place, C; Dicara, D; Ramos, AH; Lawrence, MS; Cibulskis, K; Sivachenko, A; Voet, D; Saksena, G; Stransky, N; Onofrio, RC; Winckler, W; Ardlie, K; Wagle, N; Wargo, J; Chong, K; Morton, DL; Stemke-Hale, K; Chen, G; Noble, M; Meyerson, M; Ladbury, JE; Davies, MA; Gershenwald, JE; Wagner, SN; Hoon, DS; Schadendorf, D; Lander, ES; Gabriel, SB; Getz, G; Garraway, LA; Chin, L (2012 Jul 18). “A landscape of driver mutations in melanoma.”. Cell. PMID (22817889).
- ^ Krauthammer, M; Kong, Y; Ha, BH; Evans, P; Bacchiocchi, A; McCusker, JP; Cheng, E; Davis, MJ; Goh, G; Choi, M; Ariyan, S; Narayan, D; Dutton-Regester, K; Capatana, A; Holman, EC; Bosenberg, M; Sznol, M; Kluger, HM; Brash, DE; Stern, DF; Materin, MA; Lo, RS; Mane, S; Ma, S; Kidd, KK; Hayward, NK; Lifton, RP; Schlessinger, J; Boggon, TJ; Halaban, R (2012 Jul 29). “Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma.”. Nature genetics. PMID (22842228).
- ^ Bauer, Natalie N.; Chen, Yih-Wen; Samant, Rajeev S.; Shevde, Lalita A.; Fodstad, Oystein (2007). “Rac1 activity regulates proliferation of aggressive metastatic melanoma”. Experimental Cell Research 313 (18): 3832–3839. doi:10.1016/j.yexcr.2007.08.017. ISSN 00144827.
- ^ Stallings-Mann, M. L.; Waldmann, J.; Zhang, Y.; Miller, E.; Gauthier, M. L.; Visscher, D. W.; Downey, G. P.; Radisky, E. S. et al. (2012). “Matrix Metalloproteinase Induction of Rac1b, a Key Effector of Lung Cancer Progression”. Science Translational Medicine 4 (142): 142ra95–142ra95. doi:10.1126/scitranslmed.3004062. ISSN 1946-6234.
- ^ McAllister, S. S. (2012). “Got a Light? Illuminating Lung Cancer”. Science Translational Medicine 4 (142): 142fs22–142fs22. doi:10.1126/scitranslmed.3004446. ISSN 1946-6234.
- ^ Ridley A. (2006). “Rho GTPases and actin dynamics in membrane protrusions and vesicle trafficking”. Trends Cell Biol 16 (10): 522–9. doi:10.1016/j.tcb.2006.08.006. ISSN 0962-8924. PMID (16949823).
- ^ a b Shin, O H; Exton J H (August 2001). “Differential binding of arfaptin 2/POR1 to ADP-ribosylation factors and Rac1”. Biochem. Biophys. Res. Commun. (United States) 285 (5): 1267–73. doi:10.1006/bbrc.2001.5330. ISSN 0006-291X. PMID (11478794).
- ^ Van Aelst, L; Joneson T, Bar-Sagi D (August 1996). “Identification of a novel Rac1-interacting protein involved in membrane ruffling”. EMBO J. (ENGLAND) 15 (15): 3778–86. ISSN 0261-4189. PMC 452058. PMID (8670882) .
- ^ Tarricone, C; Xiao B, Justin N, Walker P A, Rittinger K, Gamblin S J, Smerdon S J (May 2001). “The structural basis of Arfaptin-mediated cross-talk between Rac and Arf signalling pathways”. Nature (England) 411 (6834): 215–9. doi:10.1038/35075620. ISSN 0028-0836. PMID (11346801).
- ^ Shimizu, M; Wang W, Walch E T, Dunne P W, Epstein H F (June 2000). “Rac-1 and Raf-1 kinases, components of distinct signaling pathways, activate myotonic dystrophy protein kinase”. FEBS Lett. (NETHERLANDS) 475 (3): 273–7. doi:10.1016/S0014-5793(00)01692-6. ISSN 0014-5793. PMID (10869570).
- ^ Worthylake, D K; Rossman K L, Sondek J (Dec. 2000). “Crystal structure of Rac1 in complex with the guanine nucleotide exchange region of Tiam1”. Nature (England) 408 (6813): 682–8. doi:10.1038/35047014. ISSN 0028-0836. PMID (11130063).
- ^ Gao, Y; Xing J, Streuli M, Leto T L, Zheng Y (Dec. 2001). “Trp(56) of rac1 specifies interaction with a subset of guanine nucleotide exchange factors”. J. Biol. Chem. (United States) 276 (50): 47530–41. doi:10.1074/jbc.M108865200. ISSN 0021-9258. PMID (11595749).
- ^ a b Noda, Y; Takeya R, Ohno S, Naito S, Ito T, Sumimoto H (February 2001). “Human homologues of the Caenorhabditis elegans cell polarity protein PAR6 as an adaptor that links the small GTPases Rac and Cdc42 to atypical protein kinase C”. Genes Cells (England) 6 (2): 107–19. doi:10.1046/j.1365-2443.2001.00404.x. ISSN 1356-9597. PMID (11260256).
- ^ Katoh, Hironori; Negishi Manabu (July 2003). “RhoG activates Rac1 by direct interaction with the Dock180-binding protein Elmo”. Nature (England) 424 (6947): 461–4. doi:10.1038/nature01817. PMID (12879077).
- ^ Seoh, Mui Leng; Ng Chong Han, Yong Jeffery, Lim Louis, Leung Thomas (March 2003). “ArhGAP15, a novel human RacGAP protein with GTPase binding property”. FEBS Lett. (Netherlands) 539 (1–3): 131–7. doi:10.1016/S0014-5793(03)00213-8. ISSN 0014-5793. PMID (12650940).
- ^ a b Zhang, B; Chernoff J, Zheng Y (April 1998). “Interaction of Rac1 with GTPase-activating proteins and putative effectors. A comparison with Cdc42 and RhoA”. J. Biol. Chem. (UNITED STATES) 273 (15): 8776–82. doi:10.1074/jbc.273.15.8776. ISSN 0021-9258. PMID (9535855).
- ^ Ewing, Rob M; Chu Peter, Elisma Fred, Li Hongyan, Taylor Paul, Climie Shane, McBroom-Cerajewski Linda, Robinson Mark D, O'Connor Liam, Li Michael, Taylor Rod, Dharsee Moyez, Ho Yuen, Heilbut Adrian, Moore Lynda, Zhang Shudong, Ornatsky Olga, Bukhman Yury V, Ethier Martin, Sheng Yinglun, Vasilescu Julian, Abu-Farha Mohamed, Lambert Jean-Philippe, Duewel Henry S, Stewart Ian I, Kuehl Bonnie, Hogue Kelly, Colwill Karen, Gladwish Katharine, Muskat Brenda, Kinach Robert, Adams Sally-Lin, Moran Michael F, Morin Gregg B, Topaloglou Thodoros, Figeys Daniel (2007). “Large-scale mapping of human protein–protein interactions by mass spectrometry”. Mol. Syst. Biol. (England) 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID (17353931) .
- ^ Grizot, S; Fauré J, Fieschi F, Vignais P V, Dagher M C, Pebay-Peyroula E (August 2001). “Crystal structure of the Rac1-RhoGDI complex involved in nadph oxidase activation”. Biochemistry (United States) 40 (34): 10007–13. doi:10.1021/bi010288k. ISSN 0006-2960. PMID (11513578).
- ^ Lian, L Y; Barsukov I, Golovanov A P, Hawkins D I, Badii R, Sze K H, Keep N H, Bokoch G M, Roberts G C (January 2000). “Mapping the binding site for the GTP-binding protein Rac-1 on its inhibitor RhoGDI-1”. Structure (ENGLAND) 8 (1): 47–55. doi:10.1016/S0969-2126(00)00080-0. ISSN 0969-2126. PMID (10673424).
- ^ Gorvel, J P; Chang T C, Boretto J, Azuma T, Chavrier P (January 1998). “Differential properties of D4/LyGDI versus RhoGDI: phosphorylation and rho GTPase selectivity”. FEBS Lett. (NETHERLANDS) 422 (2): 269–73. doi:10.1016/S0014-5793(98)00020-9. ISSN 0014-5793. PMID (9490022).
- ^ Di-Poï, N; Fauré J, Grizot S, Molnár G, Pick E, Dagher M C (August 2001). “Mechanism of NADPH oxidase activation by the Rac/Rho-GDI complex”. Biochemistry (United States) 40 (34): 10014–22. doi:10.1021/bi010289c. ISSN 0006-2960. PMID (11513579).
- ^ Fauré, J; Dagher M C (May 2001). “Interactions between Rho GTPases and Rho GDP dissociation inhibitor (Rho-GDI)”. Biochimie (France) 83 (5): 409–14. doi:10.1016/S0300-9084(01)01263-9. ISSN 0300-9084. PMID (11368848).
- ^ Jefferies, C; Bowie A, Brady G, Cooke E L, Li X, O'Neill L A (July 2001). “Transactivation by the p65 Subunit of NF-κB in Response to Interleukin-1 (IL-1) Involves MyD88, IL-1 Receptor-Associated Kinase 1, TRAF-6, and Rac1”. Mol. Cell. Biol. (United States) 21 (14): 4544–52. doi:10.1128/MCB.21.14.4544-4552.2001. ISSN 0270-7306. PMC 87113. PMID (11416133) .
- ^ Qiu, R G; Abo A, Steven Martin G (June 2000). “A human homolog of the C. elegans polarity determinant Par-6 links Rac and Cdc42 to PKCzeta signaling and cell transformation”. Curr. Biol. (ENGLAND) 10 (12): 697–707. doi:10.1016/S0960-9822(00)00535-2. ISSN 0960-9822. PMID (10873802).
- ^ Simon, A R; Vikis H G, Stewart S, Fanburg B L, Cochran B H, Guan K L (October 2000). “Regulation of STAT3 by direct binding to the Rac1 GTPase”. Science (UNITED STATES) 290 (5489): 144–7. doi:10.1126/science.290.5489.144. ISSN 0036-8075. PMID (11021801).
- ^ Brill, S; Li S, Lyman C W, Church D M, Wasmuth J J, Weissbach L, Bernards A, Snijders A J (September 1996). “The Ras GTPase-activating-protein-related human protein IQGAP2 harbors a potential actin binding domain and interacts with calmodulin and Rho family GTPases”. Mol. Cell. Biol. (UNITED STATES) 16 (9): 4869–78. ISSN 0270-7306. PMC 231489. PMID (8756646) .
- ^ Kitamura, Y; Kitamura T, Sakaue H, Maeda T, Ueno H, Nishio S, Ohno S, Osada S i, Sakaue M, Ogawa W, Kasuga M (March 1997). “Interaction of Nck-associated protein 1 with activated GTP-binding protein Rac”. Biochem. J. (ENGLAND) 322 ( Pt 3) (Pt 3): 873–8. ISSN 0264-6021. PMC 1218269. PMID (9148763) .
- ^ Kuroda, S; Fukata M, Kobayashi K, Nakafuku M, Nomura N, Iwamatsu A, Kaibuchi K (September 1996). “Identification of IQGAP as a putative target for the small GTPases, Cdc42 and Rac1”. J. Biol. Chem. (UNITED STATES) 271 (38): 23363–7. doi:10.1074/jbc.271.38.23363. ISSN 0021-9258. PMID (8798539).
- ^ Fukata, Masaki; Watanabe Takashi, Noritake Jun, Nakagawa Masato, Yamaga Masaki, Kuroda Shinya, Matsuura Yoshiharu, Iwamatsu Akihiro, Perez Franck, Kaibuchi Kozo (June 2002). “Rac1 and Cdc42 capture microtubules through IQGAP1 and CLIP-170”. Cell (United States) 109 (7): 873–85. doi:10.1016/S0092-8674(02)00800-0. ISSN 0092-8674. PMID (12110184).
- ^ Hart, M J; Callow M G, Souza B, Polakis P (June 1996). “IQGAP1, a calmodulin-binding protein with a rasGAP-related domain, is a potential effector for cdc42Hs”. EMBO J. (ENGLAND) 15 (12): 2997–3005. ISSN 0261-4189. PMC 450241. PMID (8670801) .
- ^ Westendorf, J J (Dec. 2001). “The formin/diaphanous-related protein, FHOS, interacts with Rac1 and activates transcription from the serum response element”. J. Biol. Chem. (United States) 276 (49): 46453–9. doi:10.1074/jbc.M105162200. ISSN 0021-9258. PMID (11590143).
- ^ Miki, H; Yamaguchi H, Suetsugu S, Takenawa T (Dec. 2000). “IRSp53 is an essential intermediate between Rac and WAVE in the regulation of membrane ruffling”. Nature (England) 408 (6813): 732–5. doi:10.1038/35047107. ISSN 0028-0836. PMID (11130076).
- ^ Zhao, Chunmei; Ma Hong, Bossy-Wetzel Ella, Lipton Stuart A, Zhang Zhuohua, Feng Gen-Sheng (September 2003). “GC-GAP, a Rho family GTPase-activating protein that interacts with signaling adapters Gab1 and Gab2”. J. Biol. Chem. (United States) 278 (36): 34641–53. doi:10.1074/jbc.M304594200. ISSN 0021-9258. PMID (12819203).
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- ^ Yayoshi-Yamamoto, S; Taniuchi I, Watanabe T (September 2000). “FRL, a Novel Formin-Related Protein, Binds to Rac and Regulates Cell Motility and Survival of Macrophages”. Mol. Cell. Biol. (UNITED STATES) 20 (18): 6872–81. doi:10.1128/MCB.20.18.6872-6881.2000. ISSN 0270-7306. PMC 86228. PMID (10958683) .
推薦文献
- Benitah SA, Frye M, Glogauer M, Watt FM (2005). “Stem cell depletion through epidermal deletion of Rac1”. Science 309 (5736): 933–5. doi:10.1126/science.1113579. PMID (16081735).
- Dorseuil O, Gacon G (1997). “[Signal transduction by Rac small G proteins in phagocytes] [Signal transduction by Rac small G proteins in phagocytes]” (French). C. R. Seances Soc. Biol. Fil. 191 (2): 237–46. PMID (9255350).
- Ramakers GJ (2002). “Rho proteins, mental retardation and the cellular basis of cognition”. Trends Neurosci. 25 (4): 191–9. doi:10.1016/S0166-2236(00)02118-4. PMID (11998687).
- Esufali S, Charames S, Bapat B (2007). “Suppression of Wnt signalling leads to stabilization of Rac1 isoforms”. FEBS letters. 581 (25): 4850–4856. doi:10.1016/j.febslet.2007.09.013. PMID (17888911).
外部リンク
- (rac1 GTP-Binding Protein) - MeSH・アメリカ国立医学図書館・生命科学用語シソーラス(英語)
- RAC1 Info with links in the Cell Migration Gateway