Down-regulation of the met receptor tyrosine kinase by presenilin-dependent regulated intramembrane proteolysis.

ABSTRACT: Hepatocyte growth factor/scatter factor (HGF/SF) acts through the membrane-anchored Met receptor tyrosine kinase to induce invasive growth. Deregulation of this signaling is associated with tumorigenesis and involves, in most cases, overexpression of the receptor. We demonstrate that Met is processed in epithelial cells by presenilin-dependent regulated intramembrane proteolysis (PS-RIP) independently of ligand stimulation. The proteolytic process involves sequential cleavage by metalloproteases and the gamma-secretase complex, leading to generation of labile fragments. In normal epithelial cells, although expression of cleavable Met by PS-RIP is down-regulated, uncleavable Met displayed membrane accumulation and induced ligand-independent motility and morphogenesis. Inversely, in transfor

SUBMITTER: Foveau B 

PROVIDER: S-EPMC2675628 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature