STAT6

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External IDs	GeneCards: [1]
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Species	Human	Mouse
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Signal transducer and activator of transcription 6 (STAT6) is a human gene. 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 plays a central role in exerting IL4 mediated biological responses. It is found to induce the expression of BCL2L1/BCL-X(L), which is responsible for the anti-apoptotic activity of IL4. Knockout studies in mice suggested the roles of this gene in differentiation of T helper 2 (Th2), expression of cell surface markers, and class switch of immunoglobulins.

Interactions

STAT6 has been shown to interact with:

• CREB-binding protein,
• EP300,
• IRF4,
• NFKB1,
• Nuclear receptor coactivator 1, and
• SND1.

Pathology

• Gene fusion
  • Recurrent somatic fusions of the two genes, NGFI-A–binding protein 2 (NAB2) and STAT6, located at chromosomal region 12q13, have been identified in solitary fibrous tumors.
• Amplification
  • STAT6 is amplified in a subset of dedifferentiated liposarcoma.

See also

• Interleukin 4

Further reading

• Jiang H, Harris MB, Rothman P (Jun 2000). "IL-4/IL-13 signaling beyond JAK/STAT". The Journal of Allergy and Clinical Immunology. 105 (6 Pt 1): 1063–70. doi:10.1067/mai.2000.107604. PMID 10856136.
• Kisseleva T, Bhattacharya S, Braunstein J, Schindler CW (Feb 2002). "Signaling through the JAK/STAT pathway, recent advances and future challenges". Gene. 285 (1–2): 1–24. doi:10.1016/S0378-1119(02)00398-0. PMID 12039028.
• Hou J, Schindler U, Henzel WJ, Ho TC, Brasseur M, McKnight SL (Sep 1994). "An interleukin-4-induced transcription factor: IL-4 Stat". Science. 265 (5179): 1701–6. doi:10.1126/science.8085155. PMID 8085155.
• Takeda K, Tanaka T, Shi W, Matsumoto M, Minami M, Kashiwamura S, Nakanishi K, Yoshida N, Kishimoto T, Akira S (Apr 1996). "Essential role of Stat6 in IL-4 signalling". Nature. 380 (6575): 627–30. doi:10.1038/380627a0. PMID 8602263.
• Shimoda K, van Deursen J, Sangster MY, Sarawar SR, Carson RT, Tripp RA, Chu C, Quelle FW, Nosaka T, Vignali DA, Doherty PC, Grosveld G, Paul WE, Ihle JN (Apr 1996). "Lack of IL-4-induced Th2 response and IgE class switching in mice with disrupted Stat6 gene". Nature. 380 (6575): 630–3. doi:10.1038/380630a0. PMID 8602264.
• Kotanides H, Reich NC (Oct 1996). "Interleukin-4-induced STAT6 recognizes and activates a target site in the promoter of the interleukin-4 receptor gene". The Journal of Biological Chemistry. 271 (41): 25555–61. doi:10.1074/jbc.271.41.25555. PMID 8810328.
• Mikita T, Campbell D, Wu P, Williamson K, Schindler U (Oct 1996). "Requirements for interleukin-4-induced gene expression and functional characterization of Stat6". Molecular and Cellular Biology. 16 (10): 5811–20. doi:10.1128/mcb.16.10.5811. PMC 231582. PMID 8816495.
• Shen CH, Stavnezer J (Jun 1998). "Interaction of stat6 and NF-kappaB: direct association and synergistic activation of interleukin-4-induced transcription". Molecular and Cellular Biology. 18 (6): 3395–404. doi:10.1128/mcb.18.6.3395. PMC 108921. PMID 9584180.
• Leek JP, Hamlin PJ, Bell SM, Lench NJ (1998). "Assignment of the STAT6 gene (STAT6) to human chromosome band 12q13 by in situ hybridization". Cytogenetics and Cell Genetics. 79 (3–4): 208–9. doi:10.1159/000134723. PMID 9605853.
• Mikita T, Kurama M, Schindler U (Aug 1998). "Synergistic activation of the germline epsilon promoter mediated by Stat6 and C/EBP beta". Journal of Immunology. 161 (4): 1822–8. PMID 9712049.
• Patel BK, Keck CL, O'Leary RS, Popescu NC, LaRochelle WJ (Sep 1998). "Localization of the human stat6 gene to chromosome 12q13.3-q14.1, a region implicated in multiple solid tumors". Genomics. 52 (2): 192–200. doi:10.1006/geno.1998.5436. PMID 9782085.
• Zhu M, John S, Berg M, Leonard WJ (Jan 1999). "Functional association of Nmi with Stat5 and Stat1 in IL-2- and IFNgamma-mediated signaling". Cell. 96 (1): 121–30. doi:10.1016/S0092-8674(00)80965-4. PMID 9989503.
• McDonald C, Reich NC (Jul 1999). "Cooperation of the transcriptional coactivators CBP and p300 with Stat6". Journal of Interferon & Cytokine Research. 19 (7): 711–22. doi:10.1089/107999099313550. PMID 10454341.
• Harris MB, Chang CC, Berton MT, Danial NN, Zhang J, Kuehner D, Ye BH, Kvatyuk M, Pandolfi PP, Cattoretti G, Dalla-Favera R, Rothman PB (Oct 1999). "Transcriptional repression of Stat6-dependent interleukin-4-induced genes by BCL-6: specific regulation of iepsilon transcription and immunoglobulin E switching". Molecular and Cellular Biology. 19 (10): 7264–75. doi:10.1128/mcb.19.10.7264. PMC 84719. PMID 10490661.
• Gupta S, Jiang M, Pernis AB (Oct 1999). "IFN-alpha activates Stat6 and leads to the formation of Stat2:Stat6 complexes in B cells". Journal of Immunology. 163 (7): 3834–41. PMID 10490982.
• Gupta S, Jiang M, Anthony A, Pernis AB (Dec 1999). "Lineage-specific modulation of interleukin 4 signaling by interferon regulatory factor 4". The Journal of Experimental Medicine. 190 (12): 1837–48. doi:10.1084/jem.190.12.1837. PMC 2195723. PMID 10601358.
• Daniel C, Salvekar A, Schindler U (May 2000). "A gain-of-function mutation in STAT6". The Journal of Biological Chemistry. 275 (19): 14255–9. doi:10.1074/jbc.C000129200. PMID 10747856.
• Arinobu Y, Sugimoto R, Akaiwa M, Arima K, Otsuka T, Hamasaki N, Izuhara K (Oct 2000). "Augmentation of signal transducer and activation of transcription (STAT)6 and STAT3 expression in stimulated B and T cells". Biochemical and Biophysical Research Communications. 277 (2): 317–24. doi:10.1006/bbrc.2000.3674. PMID 11032724.
• Masuda A, Matsuguchi T, Yamaki K, Hayakawa T, Yoshikai Y (Jul 2001). "Interleukin-15 prevents mouse mast cell apoptosis through STAT6-mediated Bcl-xL expression". The Journal of Biological Chemistry. 276 (28): 26107–13. doi:10.1074/jbc.M011475200. PMID 11369758.

External links

• STAT6+Transcription+Factor at the US National Library of Medicine Medical Subject Headings (MeSH)