THE ACTIN-BINDING DOMAIN OF THE EPIDERMAL GROWTH-FACTOR RECEPTOR IS REQUIRED FOR EGF-STIMULATED TISSUE INVASION

NIH-3T3 fibroblasts expressing epidermal growth factor receptors (EGFR s) lacking the actin binding domain (ABD) were analyzed for their EGF- induced capacity to invade a bone marrow stromal cell (BMSC) monolayer , The fibroblasts display a reduction in the percentage of cytoskeleto n-associated EGFRs. Furthermore, EGF-induced tyrosine kinase activity is unaffected by the mutation, Cells expressing the mutant EGFRs hardl y invade a BMSC monolayer upon EGF stimulation in contrast to cells ex pressing wild-type EGFRs. Using the same cells no difference was obser ved in PDGF-induced invasion, which ligand was as potent in both cell types as EGF was in wild-type cells. Inhibition of both the phosphatid yl inositol-3-kinase (PI-3-K) and lipoxygenase pathways in wild-type c ells mimicked the effect of the ABD deletion. Our results point to an important role for the ABD of the EGFR in EGF-induced tissue invasion. (C) 1997 Academic Press.