Signal transducers and activators of transcription-3 binding to the fibroblast growth factor receptor is activated by receptor amplification.

ABSTRACT: Fibroblast growth factor receptors (FGFR) are cell surface tyrosine kinases that function in cell proliferation and differentiation. Aberrant FGFR signaling occurs in diverse cancers due to gene amplification, but the associated oncogenic mechanisms are poorly understood. Using a proteomics approach, we identified signal transducers and activators of transcription-3 (STAT3) as a receptor-binding partner that is mediated by Tyr(677) phosphorylation on FGFR. Binding to activated FGFR was essential for subsequent tyrosine phosphorylation and nuclear translocation of STAT3, along with activation of its downstream target genes. Tyrosine phosphorylation of STAT3 was also dependent on concomitant FGFR-dependent activity of SRC and JAK kinases. Lastly, tyrosine (but not serine) phosphorylation of

SUBMITTER: Dudka AA 

PROVIDER: S-EPMC2887080 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature