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Wikipedia

STAT3

Signal transducer and activator of transcription 3 (STAT3) is a transcription factor which in humans is encoded by the STAT3 gene. It is a member of the STAT protein family.

STAT3
Available structures
PDBOrtholog search:PDBe RCSB
List of PDB id codes

5AX3

Identifiers
AliasesSTAT3, ADMIO, APRF, HIES, signal transducer and activator of transcription 3, ADMIO1
External IDsOMIM: 102582 MGI: 103038 HomoloGene: 7960 GeneCards: STAT3
Gene location (Human)
Chr.Chromosome 17 (human)
Band17q21.2Start42,313,324 bp
End42,388,568 bp
Gene location (Mouse)
Chr.Chromosome 11 (mouse)
Band11 D|11 63.82 cMStart100,885,098 bp
End100,939,540 bp
RNA expression pattern
Bgee
Top expressed in
  • left coronary artery
  • urinary bladder
  • ovary
  • pericardium
  • upper lobe of lung
  • right ventricle
  • peritoneum
More reference expression data
BioGPS
Gene ontology
Molecular function
  • protein dimerization activity
  • GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity
  • GO:0001077, GO:0001212, GO:0001213, GO:0001211, GO:0001205 DNA-binding transcription activator activity, RNA polymerase II-specific
  • GO:0038050, GO:0004886, GO:0038051 nuclear receptor activity
  • protein phosphatase binding
  • GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding
  • GO:0001948 protein binding
  • protein kinase binding
  • DNA binding
  • sequence-specific DNA binding
  • chromatin DNA binding
  • protein homodimerization activity
  • identical protein binding
  • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific
  • signal transducer activity
  • transcription factor binding
  • CCR5 chemokine receptor binding
  • glucocorticoid receptor binding
  • Cellular component
    Biological process
    Sources:Amigo / QuickGO
    Orthologs
    SpeciesHumanMouse
    Entrez
    Ensembl
    UniProt
    RefSeq (mRNA)
    RefSeq (protein)
    Location (UCSC)Chr 17: 42.31 – 42.39 MbChr 11: 100.89 – 100.94 Mb
    PubMed search
    Wikidata

    Contents

    STAT3 is a member of the STAT protein family. In response to cytokines and growth factors, STAT3 is phosphorylated by receptor-associated Janus kinases (JAK), form homo- or heterodimers, and translocate to the cell nucleus where they act as transcription activators. Specifically, STAT3 becomes activated after phosphorylation of tyrosine 705 in response to such ligands as interferons, epidermal growth factor (EGF), Interleukin (IL-)5 and IL-6. Additionally, activation of STAT3 may occur via phosphorylation of serine 727 by Mitogen-activated protein kinases (MAPK) and through c-src non-receptor tyrosine kinase. STAT3 mediates the expression of a variety of genes in response to cell stimuli, and thus plays a key role in many cellular processes such as cell growth and apoptosis.

    STAT3-deficient mouse embryos cannot develop beyond embryonic day 7, when gastrulation begins. It appears that at these early stages of development, STAT3 activation is required for self-renewal of embryonic stem cells (ESCs). Indeed, LIF, which is supplied to murine ESC cultures to maintain their undifferentiated state, can be omitted if STAT3 is activated through some other means.

    STAT3 is essential for the differentiation of the TH17 helper T cells, which have been implicated in a variety of autoimmune diseases. During viral infection, mice lacking STAT3 in T-cells display impairment in the ability to generate T-follicular helper (Tfh) cells and fail to maintain antibody based immunity.

    STAT3 caused upregulation in E-selectin, a factor in metastasis of cancers.

    Loss-of-function mutations in the STAT3 gene result in Hyperimmunoglobulin E syndrome, associated with recurrent infections as well as disordered bone and tooth development.

    Gain-of-function mutations in the STAT3 gene have been reported to cause multi-organ early onset auto-immune diseases; such as thyroid disease, diabetes, intestinal inflammation, and low blood counts, while constitutive STAT3 activation is associated with various human cancers and commonly suggests poor prognosis. It has anti-apoptotic as well as proliferative effects.

    STAT3 can promote oncogenesis by being constitutively active through various pathways as mentioned elsewhere. A tumor suppressor role of STAT3 has also been reported. In the report on human glioblastoma tumor, or brain cancer, STAT3 was shown to have an oncogenic or a tumor suppressor role depending upon the mutational background of the tumor. A direct connection between the PTEN-Akt-FOXO axis (suppressive) and the leukemia inhibitory factor receptor beta (LIFRbeta)-STAT3 signaling pathway (oncogenic) was shown.

    Increased activity of STAT3 in cancer cells, leads to changes in the function of protein complexes that control expression of inflammatory genes, with result profound change in the secretome and the cell phenotypes, their activity in the tumor, and their capacity for metastasis.

    STAT3 has been shown to interact with:

    Niclosamide seems to inhibit the STAT3 signalling pathway.

    1. GRCh38: Ensembl release 89: ENSG00000168610 - Ensembl, May 2017
    2. GRCm38: Ensembl release 89: ENSMUSG00000004040 - Ensembl, May 2017
    3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
    4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
    5. Akira S, Nishio Y, Inoue M, Wang XJ, Wei S, Matsusaka T, Yoshida K, Sudo T, Naruto M, Kishimoto T (April 1994). "Molecular cloning of APRF, a novel IFN-stimulated gene factor 3 p91-related transcription factor involved in the gp130-mediated signaling pathway". Cell. 77 (1): 63–71. doi:10.1016/0092-8674(94)90235-6. PMID 7512451. S2CID 42211976.
    6. Tkach M, Rosemblit C, Rivas MA, Proietti CJ, Díaz Flaqué MC, Mercogliano MF, Beguelin W, Maronna E, Guzmán P, Gercovich FG, Deza EG, Elizalde PV, Schillaci R (April 2013). "p42/p44 MAPK-mediated Stat3Ser727 phosphorylation is required for progestin-induced full activation of Stat3 and breast cancer growth". Endocrine-Related Cancer. 20 (2): 197–212. doi:10.1530/ERC-12-0194. PMID 23329648.
    7. Silva CM (October 2004). "Role of STATs as downstream signal transducers in Src family kinase-mediated tumorigenesis". Oncogene. 23 (48): 8017–23. doi:10.1038/sj.onc.1208159. PMID 15489919.
    8. Lim CP, Cao X (November 2006). "Structure, function, and regulation of STAT proteins". Molecular BioSystems. 2 (11): 536–50. doi:10.1039/B606246F. PMID 17216035..
    9. Yuan ZL, Guan YJ, Wang L, Wei W, Kane AB, Chin YE (November 2004). "Central role of the threonine residue within the p+1 loop of receptor tyrosine kinase in STAT3 constitutive phosphorylation in metastatic cancer cells". Molecular and Cellular Biology. 24 (21): 9390–400. doi:10.1128/MCB.24.21.9390-9400.2004. PMC522220. PMID 15485908. 15485908.
    10. Takeda K, Noguchi K, Shi W, Tanaka T, Matsumoto M, Yoshida N, Kishimoto T, Akira S (April 1997). "Targeted disruption of the mouse Stat3 gene leads to early embryonic lethality". Proceedings of the National Academy of Sciences of the United States of America. 94 (8): 3801–4. Bibcode:1997PNAS...94.3801T. doi:10.1073/pnas.94.8.3801. PMC20521. PMID 9108058.
    11. Matsuda T, Nakamura T, Nakao K, Arai T, Katsuki M, Heike T, Yokota T (August 1999). "STAT3 activation is sufficient to maintain an undifferentiated state of mouse embryonic stem cells". The EMBO Journal. 18 (15): 4261–9. doi:10.1093/emboj/18.15.4261. PMC1171502. PMID 10428964.
    12. Yang XO, Panopoulos AD, Nurieva R, Chang SH, Wang D, Watowich SS, Dong C (March 2007). "STAT3 regulates cytokine-mediated generation of inflammatory helper T cells". The Journal of Biological Chemistry. 282 (13): 9358–63. doi:10.1074/jbc.C600321200. PMID 17277312.
    13. McIlwain DR, Grusdat M, Pozdeev VI, Xu HC, Shinde P, Reardon C, Hao Z, Beyer M, Bergthaler A, Häussinger D, Nolan GP, Lang KS, Lang PA (February 2015). "T-cell STAT3 is required for the maintenance of humoral immunity to LCMV". European Journal of Immunology. 45 (2): 418–27. doi:10.1002/eji.201445060. PMC4383653. PMID 25393615.
    14. Coppo, R.; Orso, F.; Virga, F.; Dalmasso, A.; Baruffaldi, D.; Nie, L.; Clapero, F.; Dettori, D.; Quirico, L.; Grassi, E.; Defilippi, P.; Provero, P.; Valdembri, D.; Serini, G.; Sadeghi, M. M.; Mazzone, M.; Taverna, D. (2021). "ESDN inhibits melanoma progression by blocking E-selectin expression in endothelial cells via STAT3". Cancer Letters. 510: 13–23. doi:10.1016/j.canlet.2021.04.005. hdl:2318/1791282. PMID 33862151.
    15. Levy DE, Loomis CA (October 2007). "STAT3 signaling and the hyper-IgE syndrome". The New England Journal of Medicine. 357 (16): 1655–8. doi:10.1056/NEJMe078197. PMID 17881746.
    16. Milner JD, Vogel TP, Forbes L, Ma CA, Stray-Pedersen A, Niemela JE, Lyons JJ, Engelhardt KR, Zhang Y, Topcagic N, Roberson ED, Matthews H, Verbsky JW, Dasu T, Vargas-Hernandez A, Varghese N, McClain KL, Karam LB, Nahmod K, Makedonas G, Mace EM, Sorte HS, Perminow G, Rao VK, O'Connell MP, Price S, Su HC, Butrick M, McElwee J, Hughes JD, Willet J, Swan D, Xu Y, Santibanez-Koref M, Slowik V, Dinwiddie DL, Ciaccio CE, Saunders CJ, Septer S, Kingsmore SF, White AJ, Cant AJ, Hambleton S, Cooper MA (January 2015). "Early-onset lymphoproliferation and autoimmunity caused by germline STAT3 gain-of-function mutations". Blood. 125 (4): 591–9. doi:10.1182/blood-2014-09-602763. PMC4304103. PMID 25359994.
    17. Klampfer L (March 2006). "Signal transducers and activators of transcription (STATs): Novel targets of chemopreventive and chemotherapeutic drugs". Current Cancer Drug Targets. 6 (2): 107–21. doi:10.2174/156800906776056491. PMID 16529541.
    18. Alvarez JV, Greulich H, Sellers WR, Meyerson M, Frank DA (March 2006). "Signal transducer and activator of transcription 3 is required for the oncogenic effects of non-small-cell lung cancer-associated mutations of the epidermal growth factor receptor". Cancer Research. 66 (6): 3162–8. doi:10.1158/0008-5472.CAN-05-3757. PMID 16540667.
    19. Yin W, Cheepala S, Roberts JN, Syson-Chan K, DiGiovanni J, Clifford JL (April 2006). "Active Stat3 is required for survival of human squamous cell carcinoma cells in serum-free conditions". Molecular Cancer. 5 (1): 15. doi:10.1186/1476-4598-5-15. PMC1502137. PMID 16603078.
    20. Kusaba T, Nakayama T, Yamazumi K, Yakata Y, Yoshizaki A, Inoue K, Nagayasu T, Sekine I (June 2006). "Activation of STAT3 is a marker of poor prognosis in human colorectal cancer". Oncology Reports. 15 (6): 1445–51. doi:10.3892/or.15.6.1445. PMID 16685378.
    21. de la Iglesia N, Konopka G, Puram SV, Chan JA, Bachoo RM, You MJ, Levy DE, Depinho RA, Bonni A (February 2008). "Identification of a PTEN-regulated STAT3 brain tumor suppressor pathway". Genes & Development. 22 (4): 449–62. doi:10.1101/gad.1606508. PMC2238667. PMID 18258752.
    22. Lee J, Kim JC, Lee SE, Quinley C, Kim H, Herdman S, Corr M, Raz E (May 2012). "Signal transducer and activator of transcription 3 (STAT3) protein suppresses adenoma-to-carcinoma transition in Apcmin/+ mice via regulation of Snail-1 (SNAI) protein stability". The Journal of Biological Chemistry. 22. 287 (22): 18182–9. doi:10.1074/jbc.M111.328831. PMC3365759. PMID 22496368.
    23. Musteanu M, Blaas L, Mair M, Schlederer M, Bilban M, Tauber S, Esterbauer H, Mueller M, Casanova E, Kenner L, Poli V, Eferl R (March 2010). "Stat3 is a negative regulator of intestinal tumor progression in Apc(Min) mice". Gastroenterology. 138 (3): 1003–11.e1–5. doi:10.1053/j.gastro.2009.11.049. PMID 19962983.
    24. Vlahopoulos, SA (August 2017). "Aberrant control of NF-κB in cancer permits transcriptional and phenotypic plasticity, to curtail dependence on host tissue: molecular mode". Cancer Biology & Medicine. 14 (3): 254–270. doi:10.20892/j.issn.2095-3941.2017.0029. PMC5570602. PMID 28884042.
    25. Ueda T, Bruchovsky N, Sadar MD (March 2002). "Activation of the androgen receptor N-terminal domain by interleukin-6 via MAPK and STAT3 signal transduction pathways". The Journal of Biological Chemistry. 277 (9): 7076–85. doi:10.1074/jbc.M108255200. PMID 11751884.
    26. Matsuda T, Junicho A, Yamamoto T, Kishi H, Korkmaz K, Saatcioglu F, Fuse H, Muraguchi A (April 2001). "Cross-talk between signal transducer and activator of transcription 3 and androgen receptor signaling in prostate carcinoma cells". Biochemical and Biophysical Research Communications. 283 (1): 179–87. doi:10.1006/bbrc.2001.4758. PMID 11322786.
    27. Collum RG, Brutsaert S, Lee G, Schindler C (August 2000). "A Stat3-interacting protein (StIP1) regulates cytokine signal transduction". Proceedings of the National Academy of Sciences of the United States of America. 97 (18): 10120–5. Bibcode:2000PNAS...9710120C. doi:10.1073/pnas.170192197. PMC27739. PMID 10954736.
    28. Nakashima K, Yanagisawa M, Arakawa H, Kimura N, Hisatsune T, Kawabata M, Miyazono K, Taga T (April 1999). "Synergistic signaling in fetal brain by STAT3-Smad1 complex bridged by p300". Science. 284 (5413): 479–82. doi:10.1126/science.284.5413.479. PMID 10205054.
    29. Yuan ZL, Guan YJ, Wang L, Wei W, Kane AB, Chin YE (November 2004). "Central role of the threonine residue within the p+1 loop of receptor tyrosine kinase in STAT3 constitutive phosphorylation in metastatic cancer cells". Molecular and Cellular Biology. 24 (21): 9390–400. doi:10.1128/MCB.24.21.9390-9400.2004. PMC522220. PMID 15485908.
    30. Olayioye MA, Beuvink I, Horsch K, Daly JM, Hynes NE (June 1999). "ErbB receptor-induced activation of stat transcription factors is mediated by Src tyrosine kinases". The Journal of Biological Chemistry. 274 (24): 17209–18. doi:10.1074/jbc.274.24.17209. PMID 10358079.
    31. Jung JE, Kim HS, Lee CS, Shin YJ, Kim YN, Kang GH, Kim TY, Juhnn YS, Kim SJ, Park JW, Ye SK, Chung MH (October 2008). "STAT3 inhibits the degradation of HIF-1alpha by pVHL-mediated ubiquitination". Experimental & Molecular Medicine. 40 (5): 479–85. doi:10.3858/emm.2008.40.5.479. PMC2679355. PMID 18985005.
    32. Spiekermann K, Biethahn S, Wilde S, Hiddemann W, Alves F (August 2001). "Constitutive activation of STAT transcription factors in acute myelogenous leukemia". European Journal of Haematology. 67 (2): 63–71. doi:10.1034/j.1600-0609.2001.t01-1-00385.x. PMID 11722592. S2CID 38074766.
    33. Zhang X, Wrzeszczynska MH, Horvath CM, Darnell JE (October 1999). "Interacting regions in Stat3 and c-Jun that participate in cooperative transcriptional activation". Molecular and Cellular Biology. 19 (10): 7138–46. doi:10.1128/MCB.19.10.7138. PMC84707. PMID 10490649.
    34. Sanchez-Margalet V, Martin-Romero C (July 2001). "Human leptin signaling in human peripheral blood mononuclear cells: activation of the JAK-STAT pathway". Cellular Immunology. 211 (1): 30–6. doi:10.1006/cimm.2001.1815. PMID 11585385.
    35. Yokogami K, Wakisaka S, Avruch J, Reeves SA (January 2000). "Serine phosphorylation and maximal activation of STAT3 during CNTF signaling is mediated by the rapamycin target mTOR". Current Biology. 10 (1): 47–50. doi:10.1016/S0960-9822(99)00268-7. PMID 10660304. S2CID 14181036.
    36. Kusaba H, Ghosh P, Derin R, Buchholz M, Sasaki C, Madara K, Longo DL (January 2005). "Interleukin-12-induced interferon-gamma production by human peripheral blood T cells is regulated by mammalian target of rapamycin (mTOR)". The Journal of Biological Chemistry. 280 (2): 1037–43. doi:10.1074/jbc.M405204200. PMID 15522880.
    37. Kataoka Y, Matsumura I, Ezoe S, Nakata S, Takigawa E, Sato Y, Kawasaki A, Yokota T, Nakajima K, Felsani A, Kanakura Y (November 2003). "Reciprocal inhibition between MyoD and STAT3 in the regulation of growth and differentiation of myoblasts". The Journal of Biological Chemistry. 278 (45): 44178–87. doi:10.1074/jbc.M304884200. PMID 12947115.
    38. Zhang J, Yang J, Roy SK, Tininini S, Hu J, Bromberg JF, Poli V, Stark GR, Kalvakolanu DV (August 2003). "The cell death regulator GRIM-19 is an inhibitor of signal transducer and activator of transcription 3". Proceedings of the National Academy of Sciences of the United States of America. 100 (16): 9342–7. Bibcode:2003PNAS..100.9342Z. doi:10.1073/pnas.1633516100. PMC170920. PMID 12867595.
    39. Yu Z, Zhang W, Kone BC (October 2002). "Signal transducers and activators of transcription 3 (STAT3) inhibits transcription of the inducible nitric oxide synthase gene by interacting with nuclear factor kappaB". The Biochemical Journal. 367 (Pt 1): 97–105. doi:10.1042/BJ20020588. PMC1222853. PMID 12057007.
    40. Lerner L, Henriksen MA, Zhang X, Darnell JE (October 2003). "STAT3-dependent enhanceosome assembly and disassembly: synergy with GR for full transcriptional increase of the alpha 2-macroglobulin gene". Genes & Development. 17 (20): 2564–77. doi:10.1101/gad.1135003. PMC218150. PMID 14522952.
    41. Zhang Z, Jones S, Hagood JS, Fuentes NL, Fuller GM (December 1997). "STAT3 acts as a co-activator of glucocorticoid receptor signaling". The Journal of Biological Chemistry. 272 (49): 30607–10. doi:10.1074/jbc.272.49.30607. PMID 9388192.
    42. Giraud S, Bienvenu F, Avril S, Gascan H, Heery DM, Coqueret O (March 2002). "Functional interaction of STAT3 transcription factor with the coactivator NcoA/SRC1a". The Journal of Biological Chemistry. 277 (10): 8004–11. doi:10.1074/jbc.M111486200. PMID 11773079.
    43. Kawasaki A, Matsumura I, Kataoka Y, Takigawa E, Nakajima K, Kanakura Y (May 2003). "Opposing effects of PML and PML/RAR alpha on STAT3 activity". Blood. 101 (9): 3668–73. doi:10.1182/blood-2002-08-2474. PMID 12506013.
    44. Simon AR, Vikis HG, Stewart S, Fanburg BL, Cochran BH, Guan KL (October 2000). "Regulation of STAT3 by direct binding to the Rac1 GTPase". Science. 290 (5489): 144–7. Bibcode:2000Sci...290..144S. doi:10.1126/science.290.5489.144. PMID 11021801.
    45. Hwang JH, Kim DW, Suh JM, Kim H, Song JH, Hwang ES, Park KC, Chung HK, Kim JM, Lee TH, Yu DY, Shong M (June 2003). "Activation of signal transducer and activator of transcription 3 by oncogenic RET/PTC (rearranged in transformation/papillary thyroid carcinoma) tyrosine kinase: roles in specific gene regulation and cellular transformation". Molecular Endocrinology. 17 (6): 1155–66. doi:10.1210/me.2002-0401. PMID 12637586.
    46. Schuringa JJ, Wojtachnio K, Hagens W, Vellenga E, Buys CH, Hofstra R, Kruijer W (August 2001). "MEN2A-RET-induced cellular transformation by activation of STAT3". Oncogene. 20 (38): 5350–8. doi:10.1038/sj.onc.1204715. PMID 11536047.
    47. Kim J, Kim D, Chung J (2000). "Replication protein a 32 kDa subunit (RPA p32) binds the SH2 domain of STAT3 and regulates its transcriptional activity". Cell Biology International. 24 (7): 467–73. doi:10.1006/cbir.2000.0525. PMID 10875894. S2CID 23783745.
    48. Gunaje JJ, Bhat GJ (October 2001). "Involvement of tyrosine phosphatase PTP1D in the inhibition of interleukin-6-induced Stat3 signaling by alpha-thrombin". Biochemical and Biophysical Research Communications. 288 (1): 252–7. doi:10.1006/bbrc.2001.5759. PMID 11594781.
    49. Xia L, Wang L, Chung AS, Ivanov SS, Ling MY, Dragoi AM, Platt A, Gilmer TM, Fu XY, Chin YE (August 2002). "Identification of both positive and negative domains within the epidermal growth factor receptor COOH-terminal region for signal transducer and activator of transcription (STAT) activation". The Journal of Biological Chemistry. 277 (34): 30716–23. doi:10.1074/jbc.M202823200. PMID 12070153.
    50. Morris EJ, Kawamura E, Gillespie JA, Balgi A, Kannan N, Muller WJ, Roberge M, Dedhar S (May 2017). "Stat3 regulates centrosome clustering in cancer cells via Stathmin/PLK1". Nature Communications. 8: 15289. Bibcode:2017NatCo...815289M. doi:10.1038/ncomms15289. PMC5424153. PMID 28474672.
    51. Cao X, Tay A, Guy GR, Tan YH (April 1996). "Activation and association of Stat3 with Src in v-Src-transformed cell lines". Molecular and Cellular Biology. 16 (4): 1595–603. doi:10.1128/MCB.16.4.1595. PMC231145. PMID 8657134.
    52. Chung YH, Cho NH, Garcia MI, Lee SH, Feng P, Jung JU (June 2004). "Activation of Stat3 transcription factor by Herpesvirus saimiri STP-A oncoprotein". Journal of Virology. 78 (12): 6489–97. doi:10.1128/JVI.78.12.6489-6497.2004. PMC416526. PMID 15163742.
    53. Liu L, McBride KM, Reich NC (June 2005). "STAT3 nuclear import is independent of tyrosine phosphorylation and mediated by importin-alpha3". Proceedings of the National Academy of Sciences of the United States of America. 102 (23): 8150–5. Bibcode:2005PNAS..102.8150L. doi:10.1073/pnas.0501643102. PMC1149424. PMID 15919823.
    54. Ren X, Duan L, He Q, Zhang Z, Zhou Y, Wu D, Pan J, Pei D, Ding K (2010). "Identification of Niclosamide as a New Small-Molecule Inhibitor of the STAT3 Signaling Pathway". ACS Medicinal Chemistry Letters. 1 (9): 454–9. doi:10.1021/ml100146z. PMC4007964. PMID 24900231.

    STAT3
    STAT3 Language Watch Edit Signal transducer and activator of transcription 3 STAT3 is a transcription factor which in humans is encoded by the STAT3 gene 5 It is a member of the STAT protein family STAT3Available structuresPDBOrtholog search PDBe RCSBList of PDB id codes5AX3IdentifiersAliasesSTAT3 ADMIO APRF HIES signal transducer and activator of transcription 3 ADMIO1External IDsOMIM 102582 MGI 103038 HomoloGene 7960 GeneCards STAT3Gene location Human Chr Chromosome 17 human 1 Band17q21 2Start42 313 324 bp 1 End42 388 568 bp 1 Gene location Mouse Chr Chromosome 11 mouse 2 Band11 D 11 63 82 cMStart100 885 098 bp 2 End100 939 540 bp 2 RNA expression patternBgeeTop expressed inleft coronary artery urinary bladder ovary pericardium upper lobe of lung right ventricle peritoneumMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionprotein dimerization activity GO 0001131 GO 0001151 GO 0001130 GO 0001204 DNA binding transcription factor activity GO 0001077 GO 0001212 GO 0001213 GO 0001211 GO 0001205 DNA binding transcription activator activity RNA polymerase II specific GO 0038050 GO 0004886 GO 0038051 nuclear receptor activity protein phosphatase binding GO 0000980 RNA polymerase II cis regulatory region sequence specific DNA binding GO 0001948 protein binding protein kinase binding DNA binding sequence specific DNA binding chromatin DNA binding protein homodimerization activity identical protein binding GO 0001200 GO 0001133 GO 0001201 DNA binding transcription factor activity RNA polymerase II specific signal transducer activity transcription factor binding CCR5 chemokine receptor binding glucocorticoid receptor bindingCellular componentcytoplasm mitochondrion nucleus plasma membrane nucleoplasm RNA polymerase II transcription regulator complex mitochondrial inner membrane cytosol GO 0097483 GO 0097481 postsynaptic density Schaffer collateral CA1 synapse glutamatergic synapse transcription regulator complexBiological processnegative regulation of glycolytic process protein import into nucleus regulation of transcription by RNA polymerase II transcription by RNA polymerase II response to organic substance positive regulation of gene silencing by miRNA radial glial cell differentiation stem cell population maintenance cellular response to hormone stimulus regulation of mitochondrial membrane permeability growth hormone receptor signaling pathway miRNA mediated inhibition of translation eye photoreceptor cell differentiation positive regulation of metalloendopeptidase activity temperature homeostasis cell population proliferation response to leptin response to ethanol positive regulation of Notch signaling pathway negative regulation of cell population proliferation response to cytokine regulation of transcription DNA templated glucose homeostasis negative regulation of cell death transcription DNA templated positive regulation of growth factor dependent skeletal muscle satellite cell proliferation positive regulation of transcription DNA templated negative regulation of hydrogen peroxide biosynthetic process energy homeostasis GO 0022415 viral process negative regulation of neuron death sexual reproduction phosphorylation leptin mediated signaling pathway cellular response to organic cyclic compound negative regulation of apoptotic process negative regulation of transcription by RNA polymerase II regulation of feeding behavior nervous system development positive regulation of ATP biosynthetic process intracellular receptor signaling pathway acute phase response negative regulation of neuron migration receptor signaling pathway via JAK STAT response to estradiol response to organic cyclic compound eating behavior somatic stem cell population maintenance regulation of multicellular organism growth aging response to peptide hormone cellular response to leptin stimulus regulation of cell cycle astrocyte differentiation response to drug signal transduction positive regulation of transcription by RNA polymerase II growth hormone receptor signaling pathway via JAK STAT positive regulation of gene expression negative regulation of stem cell differentiation positive regulation of cell population proliferation mRNA transcription by RNA polymerase II inflammatory response positive regulation of erythrocyte differentiation T helper 17 cell lineage commitment positive regulation of pri miRNA transcription by RNA polymerase II positive regulation of tyrosine phosphorylation of STAT protein interleukin 15 mediated signaling pathway interleukin 7 mediated signaling pathway positive regulation of angiogenesis positive regulation of vascular endothelial cell proliferation cytokine mediated signaling pathway interleukin 21 mediated signaling pathway interleukin 23 mediated signaling pathway interleukin 6 mediated signaling pathway interleukin 27 mediated signaling pathway interleukin 35 mediated signaling pathway cellular response to cytokine stimulus interleukin 9 mediated signaling pathway modulation of chemical synaptic transmission postsynapse to nucleus signaling pathway negative regulation of autophagy positive regulation of cell migration positive regulation of NF kappaB transcription factor activity defense response regulation of cell population proliferationSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez677420848EnsemblENSG00000168610ENSMUSG00000004040UniProtP40763P42227RefSeq mRNA NM 003150 NM 139276 NM 213662 NM 001369512 NM 001369513NM 001369514 NM 001369516 NM 001369517 NM 001369518 NM 001369519 NM 001369520NM 011486 NM 213659 NM 213660RefSeq protein NP 003141 NP 644805 NP 998827 NP 001356441 NP 001356442NP 001356443 NP 001356445 NP 001356446 NP 001356447 NP 001356448 NP 001356449NP 035616 NP 998824 NP 998825Location UCSC Chr 17 42 31 42 39 MbChr 11 100 89 100 94 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Function 2 Clinical significance 3 Interactions 4 References 5 Further reading 6 External linksFunction EditSTAT3 is a member of the STAT protein family In response to cytokines and growth factors STAT3 is phosphorylated by receptor associated Janus kinases JAK form homo or heterodimers and translocate to the cell nucleus where they act as transcription activators Specifically STAT3 becomes activated after phosphorylation of tyrosine 705 in response to such ligands as interferons epidermal growth factor EGF Interleukin IL 5 and IL 6 Additionally activation of STAT3 may occur via phosphorylation of serine 727 by Mitogen activated protein kinases MAPK 6 and through c src non receptor tyrosine kinase 7 8 STAT3 mediates the expression of a variety of genes in response to cell stimuli and thus plays a key role in many cellular processes such as cell growth and apoptosis 9 STAT3 deficient mouse embryos cannot develop beyond embryonic day 7 when gastrulation begins 10 It appears that at these early stages of development STAT3 activation is required for self renewal of embryonic stem cells ESCs Indeed LIF which is supplied to murine ESC cultures to maintain their undifferentiated state can be omitted if STAT3 is activated through some other means 11 STAT3 is essential for the differentiation of the TH17 helper T cells which have been implicated in a variety of autoimmune diseases 12 During viral infection mice lacking STAT3 in T cells display impairment in the ability to generate T follicular helper Tfh cells and fail to maintain antibody based immunity 13 STAT3 caused upregulation in E selectin a factor in metastasis of cancers 14 Clinical significance EditLoss of function mutations in the STAT3 gene result in Hyperimmunoglobulin E syndrome associated with recurrent infections as well as disordered bone and tooth development 15 Gain of function mutations in the STAT3 gene have been reported to cause multi organ early onset auto immune diseases such as thyroid disease diabetes intestinal inflammation and low blood counts 16 while constitutive STAT3 activation is associated with various human cancers and commonly suggests poor prognosis 17 18 19 20 It has anti apoptotic as well as proliferative effects 17 STAT3 can promote oncogenesis by being constitutively active through various pathways as mentioned elsewhere A tumor suppressor role of STAT3 has also been reported 21 22 23 In the report on human glioblastoma tumor or brain cancer STAT3 was shown to have an oncogenic or a tumor suppressor role depending upon the mutational background of the tumor A direct connection between the PTEN Akt FOXO axis suppressive and the leukemia inhibitory factor receptor beta LIFRbeta STAT3 signaling pathway oncogenic was shown Increased activity of STAT3 in cancer cells leads to changes in the function of protein complexes that control expression of inflammatory genes with result profound change in the secretome and the cell phenotypes their activity in the tumor and their capacity for metastasis 24 Interactions EditSTAT3 has been shown to interact with AR 25 26 ELP2 27 EP300 28 EGFR 29 30 HIF1A 31 JAK1 25 32 JUN 33 KHDRBS1 34 mTOR 35 36 MYOD1 37 NDUFA13 38 NFKB1 39 NR3C1 40 41 NCOA1 42 PML 43 RAC1 44 RELA 39 RET 29 45 46 RPA2 47 STAT1 32 48 49 Stathmin 50 Src 51 and TRIP10 52 KPNA4 53 Niclosamide seems to inhibit the STAT3 signalling pathway 54 References Edit a b c GRCh38 Ensembl release 89 ENSG00000168610 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000004040 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Akira S Nishio Y Inoue M Wang XJ Wei S Matsusaka T Yoshida K Sudo T Naruto M Kishimoto T April 1994 Molecular cloning of APRF a novel IFN stimulated gene factor 3 p91 related transcription factor involved in the gp130 mediated signaling pathway Cell 77 1 63 71 doi 10 1016 0092 8674 94 90235 6 PMID 7512451 S2CID 42211976 Tkach M Rosemblit C Rivas MA Proietti CJ Diaz Flaque MC Mercogliano MF Beguelin W Maronna E Guzman P Gercovich FG Deza EG Elizalde PV Schillaci R April 2013 p42 p44 MAPK mediated Stat3Ser727 phosphorylation is required for progestin induced full activation of Stat3 and breast cancer growth Endocrine Related Cancer 20 2 197 212 doi 10 1530 ERC 12 0194 PMID 23329648 Silva CM October 2004 Role of STATs as downstream signal transducers in Src family kinase mediated tumorigenesis Oncogene 23 48 8017 23 doi 10 1038 sj onc 1208159 PMID 15489919 Lim CP Cao X November 2006 Structure function and regulation of STAT proteins Molecular BioSystems 2 11 536 50 doi 10 1039 B606246F PMID 17216035 Yuan ZL Guan YJ Wang L Wei W Kane AB Chin YE November 2004 Central role of the threonine residue within the p 1 loop of receptor tyrosine kinase in STAT3 constitutive phosphorylation in metastatic cancer cells Molecular and Cellular Biology 24 21 9390 400 doi 10 1128 MCB 24 21 9390 9400 2004 PMC 522220 PMID 15485908 15485908 Takeda K Noguchi K Shi W Tanaka T Matsumoto M Yoshida N Kishimoto T Akira S April 1997 Targeted disruption of the mouse Stat3 gene leads to early embryonic lethality Proceedings of the National Academy of Sciences of the United States of America 94 8 3801 4 Bibcode 1997PNAS 94 3801T doi 10 1073 pnas 94 8 3801 PMC 20521 PMID 9108058 Matsuda T Nakamura T Nakao K Arai T Katsuki M Heike T Yokota T August 1999 STAT3 activation is sufficient to maintain an undifferentiated state of mouse embryonic stem cells The EMBO Journal 18 15 4261 9 doi 10 1093 emboj 18 15 4261 PMC 1171502 PMID 10428964 Yang XO Panopoulos AD Nurieva R Chang SH Wang D Watowich SS Dong C March 2007 STAT3 regulates cytokine mediated generation of inflammatory helper T cells The Journal of Biological Chemistry 282 13 9358 63 doi 10 1074 jbc C600321200 PMID 17277312 McIlwain DR Grusdat M Pozdeev VI Xu HC Shinde P Reardon C Hao Z Beyer M Bergthaler A Haussinger D Nolan GP Lang KS Lang PA February 2015 T cell STAT3 is required for the maintenance of humoral immunity to LCMV European Journal of Immunology 45 2 418 27 doi 10 1002 eji 201445060 PMC 4383653 PMID 25393615 Coppo R Orso F Virga F Dalmasso A Baruffaldi D Nie L Clapero F Dettori D Quirico L Grassi E Defilippi P Provero P Valdembri D Serini G Sadeghi M M Mazzone M Taverna D 2021 ESDN inhibits melanoma progression by blocking E selectin expression in endothelial cells via STAT3 Cancer Letters 510 13 23 doi 10 1016 j canlet 2021 04 005 hdl 2318 1791282 PMID 33862151 Levy DE Loomis CA October 2007 STAT3 signaling and the hyper IgE syndrome The New England Journal of Medicine 357 16 1655 8 doi 10 1056 NEJMe078197 PMID 17881746 Milner JD Vogel TP Forbes L Ma CA Stray Pedersen A Niemela JE Lyons JJ Engelhardt KR Zhang Y Topcagic N Roberson ED Matthews H Verbsky JW Dasu T Vargas Hernandez A Varghese N McClain KL Karam LB Nahmod K Makedonas G Mace EM Sorte HS Perminow G Rao VK O Connell MP Price S Su HC Butrick M McElwee J Hughes JD Willet J Swan D Xu Y Santibanez Koref M Slowik V Dinwiddie DL Ciaccio CE Saunders CJ Septer S Kingsmore SF White AJ Cant AJ Hambleton S Cooper MA January 2015 Early onset lymphoproliferation and autoimmunity caused by germline STAT3 gain of function mutations Blood 125 4 591 9 doi 10 1182 blood 2014 09 602763 PMC 4304103 PMID 25359994 a b Klampfer L March 2006 Signal transducers and activators of transcription STATs Novel targets of chemopreventive and chemotherapeutic drugs Current Cancer Drug Targets 6 2 107 21 doi 10 2174 156800906776056491 PMID 16529541 Alvarez JV Greulich H Sellers WR Meyerson M Frank DA March 2006 Signal transducer and activator of transcription 3 is required for the oncogenic effects of non small cell lung cancer associated mutations of the epidermal growth factor receptor Cancer Research 66 6 3162 8 doi 10 1158 0008 5472 CAN 05 3757 PMID 16540667 Yin W Cheepala S Roberts JN Syson Chan K DiGiovanni J Clifford JL April 2006 Active Stat3 is required for survival of human squamous cell carcinoma cells in serum free conditions Molecular Cancer 5 1 15 doi 10 1186 1476 4598 5 15 PMC 1502137 PMID 16603078 Kusaba T Nakayama T Yamazumi K Yakata Y Yoshizaki A Inoue K Nagayasu T Sekine I June 2006 Activation of STAT3 is a marker of poor prognosis in human colorectal cancer Oncology Reports 15 6 1445 51 doi 10 3892 or 15 6 1445 PMID 16685378 de la Iglesia N Konopka G Puram SV Chan JA Bachoo RM You MJ Levy DE Depinho RA Bonni A February 2008 Identification of a PTEN regulated STAT3 brain tumor suppressor pathway Genes amp Development 22 4 449 62 doi 10 1101 gad 1606508 PMC 2238667 PMID 18258752 Lee J Kim JC Lee SE Quinley C Kim H Herdman S Corr M Raz E May 2012 Signal transducer and activator of transcription 3 STAT3 protein suppresses adenoma to carcinoma transition in Apcmin mice via regulation of Snail 1 SNAI protein stability The Journal of Biological Chemistry 22 287 22 18182 9 doi 10 1074 jbc M111 328831 PMC 3365759 PMID 22496368 Musteanu M Blaas L Mair M Schlederer M Bilban M Tauber S Esterbauer H Mueller M Casanova E Kenner L Poli V Eferl R March 2010 Stat3 is a negative regulator of intestinal tumor progression in Apc Min mice Gastroenterology 138 3 1003 11 e1 5 doi 10 1053 j gastro 2009 11 049 PMID 19962983 Vlahopoulos SA August 2017 Aberrant control of NF kB in cancer permits transcriptional and phenotypic plasticity to curtail dependence on host tissue molecular mode Cancer Biology amp Medicine 14 3 254 270 doi 10 20892 j issn 2095 3941 2017 0029 PMC 5570602 PMID 28884042 a b Ueda T Bruchovsky N Sadar MD March 2002 Activation of the androgen receptor N terminal domain by interleukin 6 via MAPK and STAT3 signal transduction pathways The Journal of Biological Chemistry 277 9 7076 85 doi 10 1074 jbc M108255200 PMID 11751884 Matsuda T Junicho A Yamamoto T Kishi H Korkmaz K Saatcioglu F Fuse H Muraguchi A April 2001 Cross talk between signal transducer and activator of transcription 3 and androgen receptor signaling in prostate carcinoma cells Biochemical and Biophysical Research Communications 283 1 179 87 doi 10 1006 bbrc 2001 4758 PMID 11322786 Collum RG Brutsaert S Lee G Schindler C August 2000 A Stat3 interacting protein StIP1 regulates cytokine signal transduction Proceedings of the National Academy of Sciences of the United States of America 97 18 10120 5 Bibcode 2000PNAS 9710120C doi 10 1073 pnas 170192197 PMC 27739 PMID 10954736 Nakashima K Yanagisawa M Arakawa H Kimura N Hisatsune T Kawabata M Miyazono K Taga T April 1999 Synergistic signaling in fetal brain by STAT3 Smad1 complex bridged by p300 Science 284 5413 479 82 doi 10 1126 science 284 5413 479 PMID 10205054 a b Yuan ZL Guan YJ Wang L Wei W Kane AB Chin YE November 2004 Central role of the threonine residue within the p 1 loop of receptor tyrosine kinase in STAT3 constitutive phosphorylation in metastatic cancer cells Molecular and Cellular Biology 24 21 9390 400 doi 10 1128 MCB 24 21 9390 9400 2004 PMC 522220 PMID 15485908 Olayioye MA Beuvink I Horsch K Daly JM Hynes NE June 1999 ErbB receptor induced activation of stat transcription factors is mediated by Src tyrosine kinases The Journal of Biological Chemistry 274 24 17209 18 doi 10 1074 jbc 274 24 17209 PMID 10358079 Jung JE Kim HS Lee CS Shin YJ Kim YN Kang GH Kim TY Juhnn YS Kim SJ Park JW Ye SK Chung MH October 2008 STAT3 inhibits the degradation of HIF 1alpha by pVHL mediated ubiquitination Experimental amp Molecular Medicine 40 5 479 85 doi 10 3858 emm 2008 40 5 479 PMC 2679355 PMID 18985005 a b Spiekermann K Biethahn S Wilde S Hiddemann W Alves F August 2001 Constitutive activation of STAT transcription factors in acute myelogenous leukemia European Journal of Haematology 67 2 63 71 doi 10 1034 j 1600 0609 2001 t01 1 00385 x PMID 11722592 S2CID 38074766 Zhang X Wrzeszczynska MH Horvath CM Darnell JE October 1999 Interacting regions in Stat3 and c Jun that participate in cooperative transcriptional activation Molecular and Cellular Biology 19 10 7138 46 doi 10 1128 MCB 19 10 7138 PMC 84707 PMID 10490649 Sanchez Margalet V Martin Romero C July 2001 Human leptin signaling in human peripheral blood mononuclear cells activation of the JAK STAT pathway Cellular Immunology 211 1 30 6 doi 10 1006 cimm 2001 1815 PMID 11585385 Yokogami K Wakisaka S Avruch J Reeves SA January 2000 Serine phosphorylation and maximal activation of STAT3 during CNTF signaling is mediated by the rapamycin target mTOR Current Biology 10 1 47 50 doi 10 1016 S0960 9822 99 00268 7 PMID 10660304 S2CID 14181036 Kusaba H Ghosh P Derin R Buchholz M Sasaki C Madara K Longo DL January 2005 Interleukin 12 induced interferon gamma production by human peripheral blood T cells is regulated by mammalian target of rapamycin mTOR The Journal of Biological Chemistry 280 2 1037 43 doi 10 1074 jbc M405204200 PMID 15522880 Kataoka Y Matsumura I Ezoe S Nakata S Takigawa E Sato Y Kawasaki A Yokota T Nakajima K Felsani A Kanakura Y November 2003 Reciprocal inhibition between MyoD and STAT3 in the regulation of growth and differentiation of myoblasts The Journal of Biological Chemistry 278 45 44178 87 doi 10 1074 jbc M304884200 PMID 12947115 Zhang J Yang J Roy SK Tininini S Hu J Bromberg JF Poli V Stark GR Kalvakolanu DV August 2003 The cell death regulator GRIM 19 is an inhibitor of signal transducer and activator of transcription 3 Proceedings of the National Academy of Sciences of the United States of America 100 16 9342 7 Bibcode 2003PNAS 100 9342Z doi 10 1073 pnas 1633516100 PMC 170920 PMID 12867595 a b Yu Z Zhang W Kone BC October 2002 Signal transducers and activators of transcription 3 STAT3 inhibits transcription of the inducible nitric oxide synthase gene by interacting with nuclear factor kappaB The Biochemical Journal 367 Pt 1 97 105 doi 10 1042 BJ20020588 PMC 1222853 PMID 12057007 Lerner L Henriksen MA Zhang X Darnell JE October 2003 STAT3 dependent enhanceosome assembly and disassembly synergy with GR for full transcriptional increase of the alpha 2 macroglobulin gene Genes amp Development 17 20 2564 77 doi 10 1101 gad 1135003 PMC 218150 PMID 14522952 Zhang Z Jones S Hagood JS Fuentes NL Fuller GM December 1997 STAT3 acts as a co activator of glucocorticoid receptor signaling The Journal of Biological Chemistry 272 49 30607 10 doi 10 1074 jbc 272 49 30607 PMID 9388192 Giraud S Bienvenu F Avril S Gascan H Heery DM Coqueret O March 2002 Functional interaction of STAT3 transcription factor with the coactivator NcoA SRC1a The Journal of Biological Chemistry 277 10 8004 11 doi 10 1074 jbc M111486200 PMID 11773079 Kawasaki A Matsumura I Kataoka Y Takigawa E Nakajima K Kanakura Y May 2003 Opposing effects of PML and PML RAR alpha on STAT3 activity Blood 101 9 3668 73 doi 10 1182 blood 2002 08 2474 PMID 12506013 Simon AR Vikis HG Stewart S Fanburg BL Cochran BH Guan KL October 2000 Regulation of STAT3 by direct binding to the Rac1 GTPase Science 290 5489 144 7 Bibcode 2000Sci 290 144S doi 10 1126 science 290 5489 144 PMID 11021801 Hwang JH Kim DW Suh JM Kim H Song JH Hwang ES Park KC Chung HK Kim JM Lee TH Yu DY Shong M June 2003 Activation of signal transducer and activator of transcription 3 by oncogenic RET PTC rearranged in transformation papillary thyroid carcinoma tyrosine kinase roles in specific gene regulation and cellular transformation Molecular Endocrinology 17 6 1155 66 doi 10 1210 me 2002 0401 PMID 12637586 Schuringa JJ Wojtachnio K Hagens W Vellenga E Buys CH Hofstra R Kruijer W August 2001 MEN2A RET induced cellular transformation by activation of STAT3 Oncogene 20 38 5350 8 doi 10 1038 sj onc 1204715 PMID 11536047 Kim J Kim D Chung J 2000 Replication protein a 32 kDa subunit RPA p32 binds the SH2 domain of STAT3 and regulates its transcriptional activity Cell Biology International 24 7 467 73 doi 10 1006 cbir 2000 0525 PMID 10875894 S2CID 23783745 Gunaje JJ Bhat GJ October 2001 Involvement of tyrosine phosphatase PTP1D in the inhibition of interleukin 6 induced Stat3 signaling by alpha thrombin Biochemical and Biophysical Research Communications 288 1 252 7 doi 10 1006 bbrc 2001 5759 PMID 11594781 Xia L Wang L Chung AS Ivanov SS Ling MY Dragoi AM Platt A Gilmer TM Fu XY Chin YE August 2002 Identification of both positive and negative domains within the epidermal growth factor receptor COOH terminal region for signal transducer and activator of transcription STAT activation The Journal of Biological Chemistry 277 34 30716 23 doi 10 1074 jbc M202823200 PMID 12070153 Morris EJ Kawamura E Gillespie JA Balgi A Kannan N Muller WJ Roberge M Dedhar S May 2017 Stat3 regulates centrosome clustering in cancer cells via Stathmin PLK1 Nature Communications 8 15289 Bibcode 2017NatCo 815289M doi 10 1038 ncomms15289 PMC 5424153 PMID 28474672 Cao X Tay A Guy GR Tan YH April 1996 Activation and association of Stat3 with Src in v Src transformed cell lines Molecular and Cellular Biology 16 4 1595 603 doi 10 1128 MCB 16 4 1595 PMC 231145 PMID 8657134 Chung YH Cho NH Garcia MI Lee SH Feng P Jung JU June 2004 Activation of Stat3 transcription factor by Herpesvirus saimiri STP A oncoprotein Journal of Virology 78 12 6489 97 doi 10 1128 JVI 78 12 6489 6497 2004 PMC 416526 PMID 15163742 Liu L McBride KM Reich NC June 2005 STAT3 nuclear import is independent of tyrosine phosphorylation and mediated by importin alpha3 Proceedings of the National Academy of Sciences of the United States of America 102 23 8150 5 Bibcode 2005PNAS 102 8150L doi 10 1073 pnas 0501643102 PMC 1149424 PMID 15919823 Ren X Duan L He Q Zhang Z Zhou Y Wu D Pan J Pei D Ding K 2010 Identification of Niclosamide as a New Small Molecule Inhibitor of the STAT3 Signaling Pathway ACS Medicinal Chemistry Letters 1 9 454 9 doi 10 1021 ml100146z PMC 4007964 PMID 24900231 Further reading EditHoey T Grusby MJ 1999 STATs as mediators of cytokine induced responses Advances in Immunology 71 pp 145 62 doi 10 1016 S0065 2776 08 60401 0 ISBN 978 0 12 022471 5 PMID 9917912 Kisseleva T Bhattacharya S Braunstein J Schindler CW February 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 Joseph AM Kumar M Mitra D January 2005 Nef necessary and enforcing factor in HIV infection Current HIV Research 3 1 87 94 doi 10 2174 1570162052773013 PMID 15638726 Inghirami G Chiarle R Simmons WJ Piva R Schlessinger K Levy DE September 2005 New and old functions of STAT3 a pivotal target for individualized treatment of cancer Cell Cycle 4 9 1131 3 doi 10 4161 cc 4 9 1985 PMID 16082218 Leeman RJ Lui VW Grandis JR March 2006 STAT3 as a therapeutic target in head and neck cancer Expert Opinion on Biological Therapy 6 3 231 41 doi 10 1517 14712598 6 3 231 PMID 16503733 S2CID 3092794 Aggarwal BB Sethi G Ahn KS Sandur SK Pandey MK Kunnumakkara AB Sung B Ichikawa H December 2006 Targeting signal transducer and activator of transcription 3 for prevention and therapy of cancer modern target but ancient solution Annals of the New York Academy of Sciences 1091 1 151 69 Bibcode 2006NYASA1091 151A doi 10 1196 annals 1378 063 PMID 17341611 S2CID 814675 External links EditFactorBook STAT3 Retrieved from https en wikipedia org w index php title STAT3 amp oldid 1045344420, wikipedia, wiki, book,

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