Figure 1.

Met is stabilised by loss of Tyr-1003. (A) Activation of wild-type Met is coupled with its internalisation and ubiquitylation by CBL allowing efficient sorting to the multivesicular body (MVB), and subsequent degradation by the lysosome; (B) following exon 14 skipping however, the juxtamembrane domain, including Tyr-1003 is deleted. This prevents recruitment of CBL and thus Met ubiquitylation; as a consequence Met is not sorted to the MVB, instead being recycled back to the cell surface. Abbreviations: HGF, hepatocyte growth factor; p, phosphate; Ub, ubiquitin.