Activation of the FGF receptor underlies neurite outgrowth stimulated by L1, N-CAM, and N-cadherin.
Cell contact-dependent neurite outgrowth stimulated by CAMs requires activation of a second messenger pathway that requires the function of a tyrosine kinase upstream from calcium influx into neurons. In the present study, we present evidence that implicates activation of the fibroblast growth factor receptor (FGFR) in the pathway underlying neurite outgrowth stimulated by L1, N-CAM, and N-cadherin. We have identified a CAM homology domain in the FGF family of receptors and show that antibodies which bind to this domain specifically inhibit neurite outgrowth stimulated by the above CAMs. We also show that synthetic peptides derived from this domain can differentially and specifically inhibit neurite outgrowth stimulated by L1, N-CAM, and N-cadherin. In addition, a soluble L1-Fc chimera is shown to stimulate an increase in phosphotyrosine on the same set of neuronal proteins that are phosphorylated following activation of the FGFR with basic FGF.
Williams
E J
EJ
Department of Experimental Pathology, United Medical School, Guy's Hospital, London, England.
Furness
J
J
Walsh
F S
FS
Doherty
P
P
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology; D015820:Cadherins / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000235:genetics; D015816:Cell Adhesion Molecules, Neuronal / Q000494:pharmacology*; D002678:Chimera; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D007141:Immunoglobulin Fc Fragments; D039841:Leukocyte L1 Antigen Complex; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology; D010766:Phosphorylation; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D017385:Sequence Homology; D014443:Tyrosine / Q000378:metabolism
D000906:Antibodies; D015820:Cadherins; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D007141:Immunoglobulin Fc Fragments; D039841:Leukocyte L1 Antigen Complex; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D017468:Receptors, Fibroblast Growth Factor; D014443:Tyrosine; D005346:Fibroblast Growth Factors