Met receptor tyrosine kinase: enhanced signaling through adapter proteins

KA Furge, YW Zhang, GF Vande Woude - Oncogene, 2000 - nature.com
KA Furge, YW Zhang, GF Vande Woude
Oncogene, 2000nature.com
The Met receptor tyrosine kinase is the prototypic member of a small subfamily of growth
factor receptors that when activated induce mitogenic, motogenic, and morphogenic cellular
responses. The ligand for Met is hepatocyte growth factor/scatter factor (HGF/SF) and while
normal HGF/SF-Met signaling is required for embryonic development, abnormal Met
signaling has been strongly implicated in tumorigenesis, particularly in the development of
invasive and metastatic phenotypes. Following ligand binding and autophosphorylation, Met …
Abstract
The Met receptor tyrosine kinase is the prototypic member of a small subfamily of growth factor receptors that when activated induce mitogenic, motogenic, and morphogenic cellular responses. The ligand for Met is hepatocyte growth factor/scatter factor (HGF/SF) and while normal HGF/SF-Met signaling is required for embryonic development, abnormal Met signaling has been strongly implicated in tumorigenesis, particularly in the development of invasive and metastatic phenotypes. Following ligand binding and autophosphorylation, Met transmits intercellular signals using a unique multisubstrate docking site present within the C-terminal end of the receptor. The multisubstrate docking site mediates the binding of several adapter proteins such as Grb2, SHC, Crk/CRKL, and the large adapter protein Gab1. These adapter proteins in turn recruit several signal transducing proteins to form an intricate signaling complex. Analysis of how these adapter proteins bind to the Met receptor and what signal transducers they recruit have led to more substantial models of HGF/SF-Met signal transduction and have uncovered new potential pathways that may be involved into Met mediated tumor cell invasion and metastasis.
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