ACTIVATION OF THE FGF RECEPTOR UNDERLIES NEURITE OUTGROWTH STIMULATEDBY L1, N-CAM, AND N-CADHERIN

Cell contact-dependent neurite outgrowth stimulated by CAMs requires a ctivation of a second messenger pathway that requires the function of a tyrosine kinase upstream from calcium influx into neurons. In the pr esent study, we present evidence that implicates activation of the fib roblast growth factor receptor (FGFR) in the pathway underlying neurit e outgrowth stimulated by L1, N-CAM, and N-cadherin. We have identifie d a CAM homology domain in the FGF family of receptors and show that a ntibodies which bind to this domain specifically inhibit neurite outgr owth stimulated by the above CAMs. We also show that synthetic peptide s derived from this domain can differentially and specifically inhibit neurite outgrowth stimulated by L1, N-CAM, and N-cadherin. In additio n, a soluble L1-Fc chimera is shown to stimulate an increase in phosph otyrosine on the same set of neuronal proteins that are phosphorylated following activation of the FGFR with basic FGF.