Decorin is a novel antagonistic ligand of the Met receptor.

Decorin, a member of the small leucine-rich proteoglycan gene family, impedes tumor cell growth by down-regulating the epidermal growth factor receptor. Decorin has a complex binding repertoire, thus, we predicted that decorin would modulate the bioactivity of other tyrosine kinase receptors. We discovered that decorin binds directly and with high ...
affinity (K(d) = approximately 1.5 nM) to Met, the receptor for hepatocyte growth factor (HGF). Binding of decorin to Met is efficiently displaced by HGF and less efficiently by internalin B, a bacterial Met ligand. Interaction of decorin with Met induces transient receptor activation, recruitment of the E3 ubiquitin ligase c-Cbl, and rapid intracellular degradation of Met (half-life = approximately 6 min). Decorin suppresses intracellular levels of beta-catenin, a known downstream Met effector, and inhibits Met-mediated cell migration and growth. Thus, by antagonistically targeting multiple tyrosine kinase receptors, decorin contributes to reduction in primary tumor growth and metastastic spreading.
Mesh Terms:
Binding, Competitive, Cell Proliferation, Decorin, Extracellular Matrix Proteins, Half-Life, HeLa Cells, Humans, Ligands, Neoplasm Metastasis, Neoplasms, Protein Binding, Proteoglycans, Proto-Oncogene Proteins c-cbl, Proto-Oncogene Proteins c-met, beta Catenin
J. Cell Biol.
Date: May. 18, 2009
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