Meta-Biol

• Pathways

Activation of TRKA by NGF triggers STAT3 phosphorylation at Ser-727, and enhances the DNA binding and transcriptional activities of STAT3. Ser-727 phosphorylation of STAT3 begins within 5 min, and the levels of Ser(P) STAT3 remain elevated up to 30 min of NGF stimulation. Ser(P) STAT3 was localized to the cytoplasm, nuclei, and growth cones of neurites. Although the mechanisms by which STAT3 is activated by neurotrophins remaines unknown, phosphorylation of STAT3 at serine 727 might function as a convergent point for several signaling pathways triggered by Trk activation. Inhibition of STAT3 expression was found to attenuate NGF-induced transcription of immediate early genes, to suppress NGF-induced cyclin D1 expression, and to decrease BDNF-promoted neurite outgrowth in hippocampal neurons. The IL-37b:IL18R1:SIGIRR complex can facilitate the activation phosphorylation of STAT3 (Nold-Petry C A et al., 2015).