STAT5A
Signal transducer and activator of transcription 5A is a protein that in humans is encoded by the STAT5A gene.[1][2] STAT5A orthologs [3] have been identified in several placentals for which complete genome data are available.
The protein encoded by this gene is a member of the STAT family of transcription factors. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. This protein is activated by, and mediates the responses of many cell ligands, such as IL2, IL3, IL7 GM-CSF, erythropoietin, thrombopoietin, and different growth hormones. Activation of this protein in myeloma and lymphoma associated with a TEL/JAK2 gene fusion is independent of cell stimulus and has been shown to be essential for the tumorigenesis. The mouse counterpart of this gene is found to induce the expression of BCL2L1/BCL-X(L), which suggests the antiapoptotic function of this gene in cells.[4]
Interactions
STAT5A has been shown to interact with:
See also
References
- ^ Hou J, Schindler U, Henzel WJ, Wong SC, McKnight SL (May 1995). "Identification and purification of human Stat proteins activated in response to interleukin-2". Immunity 2 (4): 321–9. doi:10.1016/1074-7613(95)90140-X. PMID 7719937.
- ^ Lin JX, Mietz J, Modi WS, John S, Leonard WJ (Jul 1996). "Cloning of human Stat5B. Reconstitution of interleukin-2-induced Stat5A and Stat5B DNA binding activity in COS-7 cells". J Biol Chem 271 (18): 10738–44. doi:10.1074/jbc.271.18.10738. PMID 8631883.
- ^ "OrthoMaM phylogenetic marker: STAT5A coding sequence". http://www.orthomam.univ-montp2.fr/orthomam/data/cds/detailMarkers/ENSG00000126561_STAT5A.xml.
- ^ "Entrez Gene: STAT5A signal transducer and activator of transcription 5A". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6776.
- ^ Ota, J; Kimura F, Sato K, Wakimoto N, Nakamura Y, Nagata N, Suzu S, Yamada M, Shimamura S, Motoyoshi K (Nov. 1998). "Association of CrkL with STAT5 in hematopoietic cells stimulated by granulocyte-macrophage colony-stimulating factor or erythropoietin". Biochem. Biophys. Res. Commun. (UNITED STATES) 252 (3): 779–86. doi:10.1006/bbrc.1998.9445. ISSN 0006-291X. PMID 9837784.
- ^ a b Schulze, Waltraud X; Deng Lei, Mann Matthias (2005). "Phosphotyrosine interactome of the ErbB-receptor kinase family". Mol. Syst. Biol. (England) 1 (1): 2005.0008. doi:10.1038/msb4100012. PMC 1681463. PMID 16729043. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1681463.
- ^ Olayioye, M A; Beuvink I, Horsch K, Daly J M, Hynes N E (Jun. 1999). "ErbB receptor-induced activation of stat transcription factors is mediated by Src tyrosine kinases". J. Biol. Chem. (UNITED STATES) 274 (24): 17209–18. doi:10.1074/jbc.274.24.17209. ISSN 0021-9258. PMID 10358079.
- ^ Williams, Christopher C; Allison June G, Vidal Gregory A, Burow Matthew E, Beckman Barbara S, Marrero Luis, Jones Frank E (Nov. 2004). "The ERBB4/HER4 receptor tyrosine kinase regulates gene expression by functioning as a STAT5A nuclear chaperone". J. Cell Biol. (United States) 167 (3): 469–78. doi:10.1083/jcb.200403155. ISSN 0021-9525. PMC 2172499. PMID 15534001. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2172499.
- ^ Chin, H; Nakamura N, Kamiyama R, Miyasaka N, Ihle J N, Miura O (Dec. 1996). "Physical and functional interactions between Stat5 and the tyrosine-phosphorylated receptors for erythropoietin and interleukin-3". Blood (UNITED STATES) 88 (12): 4415–25. ISSN 0006-4971. PMID 8977232.
- ^ a b Fujitani, Y; Hibi M, Fukada T, Takahashi-Tezuka M, Yoshida H, Yamaguchi T, Sugiyama K, Yamanaka Y, Nakajima K, Hirano T (Feb. 1997). "An alternative pathway for STAT activation that is mediated by the direct interaction between JAK and STAT". Oncogene (ENGLAND) 14 (7): 751–61. doi:10.1038/sj.onc.1200907. ISSN 0950-9232. PMID 9047382.
- ^ Barahmand-Pour, F; Meinke A, Groner B, Decker T (May. 1998). "Jak2-Stat5 interactions analyzed in yeast". J. Biol. Chem. (UNITED STATES) 273 (20): 12567–75. doi:10.1074/jbc.273.20.12567. ISSN 0021-9258. PMID 9575217.
- ^ Pircher, T J; Petersen H, Gustafsson J A, Haldosén L A (Apr. 1999). "Extracellular signal-regulated kinase (ERK) interacts with signal transducer and activator of transcription (STAT) 5a". Mol. Endocrinol. (UNITED STATES) 13 (4): 555–65. doi:10.1210/me.13.4.555. ISSN 0888-8809. PMID 10194762.
- ^ Dinerstein-Cali, H; Ferrag F, Kayser C, Kelly P A, Postel-Vinay M (Aug. 2000). "Growth hormone (GH) induces the formation of protein complexes involving Stat5, Erk2, Shc and serine phosphorylated proteins". Mol. Cell. Endocrinol. (IRELAND) 166 (2): 89–99. doi:10.1016/S0303-7207(00)00277-X. ISSN 0303-7207. PMID 10996427.
- ^ Zhu, M; John S, Berg M, Leonard W J (Jan. 1999). "Functional association of Nmi with Stat5 and Stat1 in IL-2- and IFNgamma-mediated signaling". Cell (UNITED STATES) 96 (1): 121–30. doi:10.1016/S0092-8674(00)80965-4. ISSN 0092-8674. PMID 9989503.
- ^ Yu, C L; Jin Y J, Burakoff S J (Jan. 2000). "Cytosolic tyrosine dephosphorylation of STAT5. Potential role of SHP-2 in STAT5 regulation". J. Biol. Chem. (UNITED STATES) 275 (1): 599–604. doi:10.1074/jbc.275.1.599. ISSN 0021-9258. PMID 10617656.
- ^ Chughtai, Naila; Schimchowitsch Sarah, Lebrun Jean-Jacques, Ali Suhad (Aug. 2002). "Prolactin induces SHP-2 association with Stat5, nuclear translocation, and binding to the beta-casein gene promoter in mammary cells". J. Biol. Chem. (United States) 277 (34): 31107–14. doi:10.1074/jbc.M200156200. ISSN 0021-9258. PMID 12060651.
Further reading
PDB gallery
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1y1u: Structure of unphosphorylated STAT5a
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