Regulatory circuits of STAT3 signaling (Homo sapiens)

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STAT3 activation works through phosphorylation on at tyrosine 705 by a variety of adaptor kinases (JAK1, JAK2, JAK3, TYK2, SRC), resulting in dimers of STAT3 that translocates into the nucleus. Those adaptor kinases can be activated by a variety of receptors in response to cytokines or growth factors. Besides, an additional phosphate group can be added at serine 727 on each STAT3 (by MAPKs, mTOR, PKC), which enhances the transcriptional activity of STAT3 or directs STAT3 towards the mitochondria. Inside the nucleus, the STAT3 dimers are regulated by a variety of modifying factors, such as acetylation at lysine 685 by histone acetyltransferases, methylation at lysine 140 by histone methyltransferases to favor or impair STAT3 transcriptional activity, respectively. Other regulators of STAT3 include phosphatases (such as PTPRD, SOCS3, TRIM28, PIAS3) and miRNAs.