STAT3 signaling pathway: STAT3 activation is initiated by upstream activity including ligand binding by (a) cytokines (IL-6 and non-IL-6 family members), (b) growth factors (EGF, FGF, etc

STAT3 signaling pathway: STAT3 activation is initiated by upstream activity including ligand binding by (a) cytokines (IL-6 and non-IL-6 family members), (b) growth factors (EGF, FGF, etc.) to respective receptor-linked kinases, and (c) non-receptor-linked kinases (Scr, ABL). This triggers JAK activation through phosphorylation (p), with subsequent receptor tyrosine phosphorylation and STAT3 phosphorylation at Tyr705. Activated STAT3 forms homodimers which translocate to the nucleus, bind consensus DNA, and regulate the transcription of target genes. Three main endogenous proteins negatively regulate the physiologic activation of the STAT3 signaling pathway; SOCS (suppressor of cytokine signaling), PTPs (protein tyrosine phosphatase), and PIAS (protein inhibitor of activated STAT). SOCS and PTPs interact directly with respective tyrosine kinase receptors and JAK. SOCS block recruitment of STAT3 and inhibit JAK kinase activity while PTPs dephosphorylate related JAK and can directly dephosphorylate STAT3 dimers. PIAS prevents STAT3 dimers from binding DNA. Created with BioRender.com

Publication

Exploring Novel Frontiers: Leveraging STAT3 Signaling for Advanced Cancer Therapeutics (2024) Taiwo Adesoye, et al. Cancers (Basel). 2024 Feb;16(3). Figure: F2. Homo sapiens

Disease mentions