Impact of a newly identified MET receptor tyrosine kinase phosphorylation site on MET-mediated physiologic and oncogenic signaling
MET, the tyrosine kinase receptor for hepatocyte growth factor, activates a wide range of different cellular signaling pathways, including those involved in proliferation, motility, migration, and invasion. Apart from promoting biological features that are associated with tumor growth and progression, accumulating data suggest that MET signaling may protect tumor cells from DNA damage, conceivably by signaling through the DNA damage response. We have identified a previously unreported phosphorylation site on MET, which is present in the context of a phosphorylation motif recognized by DNA damage master kinases. The goal of this Swiss National Science Foundation-funded project is to dissect the nature, function, and regulation of the novel MET phosphorylation site in the context of its physiological as well as oncogenic signaling by employing distinct in vitro and in vivo models.