MET activates STAT3

MET activates STAT3 The STAT3 transcription factor binds to activated MET through phosphorylated tyrosine residue Y1356 of MET. STAT3 may also bind to activated MET indirectly through GAB1, but this interaction has not been studied in detail. Activated MET induces phosphorylation of STAT3 at Y705, triggering STAT3 dimerization and nuclear translocation (Schaper et al. 1997, Boccaccio et al. 1998, Zhang et al. 2002, Cramer et al. 2005). Endocytosis of MET and interaction with STAT3 at endosomes may be required for sustained STAT3 phosphorylation in response to HGF stimulation (Kermorgant and Parker 2008). Activated SRC may also contribute to phosphorylation of STAT3 at Y705. STAT3 may promote HGF transcription in a SRC-dependent way, but this autocrine HGF loop may be limited to breast cancer cells (Wojcik et al. 2006, Sam et al. 2007). MET-mediated activation of STAT3 is implicated in anchorage independent cell growth and invasiveness downstream of HGF (Zhang et al. 2002, Cramer et al. 2005). MET can also interact with STAT1A, STAT1B and STAT5, but the biological importance of these interactions is not known (Runge et al. 1999).