Activation and regulation of the STAT3 signaling pathway

Activation and regulation of the STAT3 signaling pathway. The STAT3 signaling pathway is turned on by the activation of cell surface receptor (growth factor or cytokine receptors) leading to recruitment and activation of JAK-family of proteins, which in turn recruits and phosphorylates STAT3. STAT3 can also be directly phosphorylated by non-tyrosine kinase receptors (Src or c-abl). Phosphorylated STAT3 homodimerizes and translocates to the nucleus where it regulates gene expression. The signaling pathway can be switched off by the actions of a phosphatase which dephosphorylates STAT3 and prevents dimer formation. Also, PIAS and SOCS family of protein can directly compete with STAT3 for either binding opportunities with the activating receptor or for dimerization and translocation into the nucleus. STAT3, signal transducers and activators of transcription 3; JAK, Janus kinase; SOCS, suppressors of cytokine signaling; PTP, protein-tyrosine phosphatase; PIAS, protein inhibitor of activated STATs.

Publication

Role of STAT3 in Transformation and Drug Resistance in CML. (2012) Rajesh R. Nair, et al. Front Oncol. 2012;2:30. Figure: F1. Mus musculus

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