Function: Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF and other growth factors. May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4. Binds to the interleukin-6 (IL-6)-responsive elements identified in the promoters of various acute-phase protein genes. Activated by IL31 through IL31RA. STAT3B interacts with the N-terminal part of JUN to activate such promoters in a cooperative way. Cytoplasmic STAT3 represses macroautophagy by inhibiting EIF2AK2/PKR activity. Plays an important role in host defense in methicillin-resistant S.aureus lung infection by regulating the expression of the antimicrobial lectin REG3G. Ref.14 Ref.23 Ref.24
Subunit structure: Forms a homodimer or a heterodimer with a related family member (at least STAT1). Interacts with IL31RA, NCOA1, PELP1, SIPAR, SOCS7, STATIP1 and TMF1. Interacts with IL23R in presence of IL23. Interacts (via SH2 domain) with NLK. Interacts with KPNA4 and KPNA5; KPNA4 may be the primary mediator of nuclear import. Interacts with CAV2; the interaction is increased on insulin-induced tyrosine phosphorylation of CAV2 and leads to STAT3 activation. Interacts with ARL2BP; interaction is enhanced with ARL2. Binds to CDK9 when activated and nuclear
By similarity. Interacts with ARL2BP; the interaction is enhanced by LIF and JAK1 expression. Interacts with NEK6. Interacts with BMX
By similarity. Interacts with ZIPK/DAPK3
By similarity. Interacts with PIAS3; the interaction occurs on stimulation by IL6, CNTF or OSM and inhibits the DNA binding activity of STAT3. Interacts with STMN3, antagonizing its microtubule-destabilizing activity. Interacts with the 'Lys-129' acetylated form of BIRC5/survivin
By similarity. Interacts with FER. Interacts (via SH2 domain) with EIF2AK2/PKR (via the kinase catalytic domain)
By similarity. Ref.10 Ref.11 Ref.12 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.21
Subcellular location: Cytoplasm. Nucleus. Note: Predominantly present in the cytoplasm without stimuli. Upon leukemia inhibitory factor (LIF) stimulation, accumulates in the nucleus. The complex composed of BART and ARL2 plays an important role in the nuclear translocation and retention of STAT3
By similarity. Shuttles between the nucleus and the cytoplasm. Translocated into the nucleus upon tyrosine phosphorylation and dimerization, in response to signaling by activated FGFR1, FGFR2, FGFR3 or FGFR4. Constitutive nuclear presence is independent of tyrosine phosphorylation. Ref.14 Ref.16
Tissue specificity: STAT3A is seen in the liver, spleen, and kidney. STAT3B is also detected in the liver, although in a much less abundant manner. Expressed in the lung and an increase in expression levels seen during methicillin-resistant S.aureus infection. Ref.24
Post-translational modification: Activated through tyrosine phosphorylation by BMX. Tyrosine phosphorylated in response to IL6, IL11, CNTF, LIF, KITLG/SCF, CSF1, EGF, PDGF, IFN-alpha and OSM. Activated KIT promotes phosphorylation on tyrosine residues and subsequent translocation to the nucleus. Tyrosine phosphorylated in response to constitutively activated FGFR1, FGFR2, FGFR3 and FGFR4. Phosphorylated on serine upon DNA damage, probably by ATM or ATR. Serine phosphorylation is important for the formation of stable DNA-binding STAT3 homodimers and maximal transcriptional activity. ARL2BP may participate in keeping the phosphorylated state of STAT3 within the nucleus. Tyrosine phosphorylated upon stimulation with EGF. Upon LPS challenge, phosphorylated within the nucleus by IRAK1
By similarity. Upon UV-A treatment, phosphorylated on Ser-727 by RPS6KA5
By similarity. Dephosphorylation on tyrosine residues by PTPN2 negatively regulates IL6/interleukin-6 signaling
By similarity. Phosphoryation at Tyr-705 by FER or PTK6 leads to an increase of its transcriptional activity. Ref.9 Ref.11 Ref.13 Ref.14 Ref.15 Ref.21 Ref.22 Ref.24
Miscellaneous: Involved in the gp130-mediated signaling pathway.
Sequence similarities: Belongs to the transcription factor STAT family.Contains 1 SH2 domain.
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