Decorin is a biological ligand for the epidermal growth factor receptor

Ectopic expression of decorin induces profound cytostatic effects in transf ormed cells with diverse histogenetic backgrounds. The mechanism of action has only recently begun to be elucidated. Exogenous decorin activates the e pidermal growth factor (EGF) receptor, thereby triggering a signaling casca de that leads to phosphorylation of mitogen-activated protein (MAP) kinase, induction of p21, and growth suppression. In this study we demonstrate a d irect interaction of decorin with the EGF receptor. Binding of decorin indu ces dimerization of the EGF receptor and rapid and sustained phosphorylatio n of MAP kinase in squamous carcinoma cells. In a cell-free system, decorin induces autophosphorylation of purified EGF receptor by activating the rec eptor tyrosine kinase and can also act as a substrate for the EGF receptor kinase itself. Using radioligand binding assays we show that both immobiliz ed and soluble decorin bind to the EGF receptor ectodomain or to purified E GF receptor. The binding is mediated by the protein core and has relatively low affinity (K-d similar to 87 nM). Thus, decorin should be considered as a novel biological ligand for the EGF receptor, an interaction that could regulate cell growth during remodeling and cancer growth.