STAT3

From Wikipedia, the free encyclopedia

STAT3 bound to DNA
signal transducer and activator of transcription 3 (acute-phase response factor)
Identifiers
Symbol STAT3
HUGO 11364
Entrez 6774
OMIM 102582
RefSeq NM_139276
UniProt P40763
Other data
Locus Chr. 17 q21

STAT3 is tyrosine-phosphorylated and activated by a number of kinases. The binding of IL-6 family cytokines (including IL-6, oncostatin M and leukemia inhibitory factor) to the gp130 receptor triggers STAT3 phosphorylation by JAK2. EGF-R and certain other receptor tyrosine kinases, such as c-MET phosphorylate STAT3 in response to their ligands.[1] STAT3 is also a target of the c-src non-receptor tyrosine kinase.[2]

STAT3-deficient mouse embryos can not develop beyond embryonic day 7 (E7.0), when gastrulation initiates.[3] 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 ESC cultures to maintain their undifferentiated state, can be omitted if STAT3 is activated through some other means.[4]

Constitutive STAT3 activation is associated with various human cancers and commonly suggests poor prognosis.[5][6][7][8] It has anti-apoptotic as well as proliferative effects.[5]

  1. ^ Yuan ZL, Guan YJ, Wang L, Wei W, Kane AB and Chin YE (2004) "Central role of the threonine residue within the p+1 loop of receptor tyrosine kinase in STAT3 constitutive phosphorylation in metastatic cancer cells" in Mol Cell Biol Volume 24 (21), pages 9390-9400. Entrez PubMed 15485908
  2. ^ Silva CM (2004) "Role of STATs as downstream signal transducers in Src family kinase-mediated tumorigenesis" in Oncogene Volume 23 (48), pages 8017-8023. Entrez PubMed 15489919
  3. ^ Takeda K, Noguchi K, Shi W, Tanaka T, Matsumoto M, Yoshida N, Kishimoto T and Akira S (1997) "Targeted disruption of the mouse Stat3 gene leads to early embryonic lethality" in PNAS Volume 94 (8), pages 3801-3084. Entrez PubMed 9108058
  4. ^ Matsuda T, Nakamura T, Nakao K, Arai T, Katsuki M, Heike T and Yokota T (1999) "STAT3 activation is sufficient to maintain an undifferentiated state of mouse embryonic stem cells" in EMBO J Volume 18 (15), pages 4261-4269. Entrez PubMed 10428964
  5. ^ a b Klampfer L (2006) "Signal transducers and activators of transcription (STATs): Novel targets of chemopreventive and chemotherapeutic drugs" in Curr Cancer Drug Targets Volume 6 (2), pages 107-121. Entrez PubMed 16529541
  6. ^ Alvarez JV, Greulich H, Sellers WR, Meyerson M and Frank DA (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" in Cancer Res Volume 66 (6), pages 3162-3168. Entrez PubMed 16540667
  7. ^ Yin W, Cheepala S, Roberts JN, Syson-Chan K, Digiovanni J and Clifford JL (2006) "Active Stat3 is required for survival of human squamous cell carcinoma cells in serum-free conditions" in Mol Cancer Volume 5 (1), article number 15. Entrez PubMed 16603078
  8. ^ Kusaba T, Nakayama T, Yamazumi K, Yakata Y, Yoshizaki A, Inoue K, Nagayasu T and Sekine I (2006) "Activation of STAT3 is a marker of poor prognosis in human colorectal cancer" in Oncol Rep Volume 15 (6), pages 1445-1451. Entrez PubMed 16685378
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Transcription factors and intracellular receptors

CAP - CBF - E2F - KlF - Nanog - NF-kB - Oct-4 - P300/CBP - PIT-1 - Rho/Sigma - R-SMAD - Sox2 - Sp1 - STAT (STAT1, STAT3, STAT5)

Basic-helix-loop-helix: AhR - HIF - MYC - Twist - Myogenic regulatory factors (MyoD, Myogenin, MYF5, MYF6)

Basic leucine zipper: C/EBP - CREB - AP-1

Basic helix-loop-helix leucine zipper: MITF - SREBP

Nuclear receptors: subfamily 1 (Thyroid hormone, RAR, PPAR, LXR, FXR, Calcitriol, PXR, CAR) - subfamily 2 (HNF4, RXR) - subfamily 3/Steroid hormone (Estrogen, Estrogen related, Glucocorticoid, Mineralocorticoid, Progesterone, Androgen) - subfamily 0 (NR0B1)

v • d • e
Signal transduction, carrier proteins: adaptor proteins

14-3-3 - Caveolin - Cortactin - Death Inducing Signaling Complex - Interferon regulatory factors - Paxillin - PIAS - SMAD - SOCS - STAT (STAT1, STAT3, STAT5)

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