title: The fibroblast growth factor receptor (FGFR) agonist FGF1 and the neural cell adhesion molecule-derived peptide FGL activate FGFR substrate 2alpha differently.
abstract: Activation of fibroblast growth factor (FGF) receptors (FGFRs) both by FGFs and by the neural cell adhesion molecule (NCAM) is crucial in the development and function of the nervous system. We found that FGFR substrate 2alpha (FRS2alpha), Src homologous and collagen A (ShcA), and phospholipase-Cgamma (PLCgamma) were all required for neurite outgrowth from cerebellar granule neurons (CGNs) induced by FGF1 and FGL (an NCAM-derived peptide agonist of FGFR1). Like FGF1, FGL induced tyrosine phosphorylation of FGFR1, FRS2alpha, ShcA, and PLCgamma in a time- and dose-dependent manner. However, the activation of FRS2alpha by FGL was significantly lower than the activation by FGF1, indicating a differential signaling profile induced by NCAM compared with the cognate growth factor.
authors.affiliation: Protein Laboratory, Department of Neuroscience and Pharmacology, Panum Institute, University of Copenhagen, Blegdamsvej 3C, Building 24.2, Copenhagen N, DK-2200, Denmark.
authors.forename: Yongshuo
authors.initials: Y
authors.lastname: Chen
authors.forename: Shizhong
authors.initials: S
authors.lastname: Li
authors.forename: Vladimir
authors.initials: V
authors.lastname: Berezin
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bock
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D049108:Cell Enlargement; D002478:Cells, Cultured; D002531:Cerebellum / Q000502:physiology*; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism*; D008959:Models, Neurological; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D016501:Neurites / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D051966:Phospholipase C gamma / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D017468:Receptors, Fibroblast Growth Factor / Q000819:agonists / Q000378:metabolism; D055765:Shc Signaling Adaptor Proteins / Q000378:metabolism; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D013997:Time Factors; D014443:Tyrosine / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C488618:NCAM protein (681-695), human; D019006:Neural Cell Adhesion Molecules; D017468:Receptors, Fibroblast Growth Factor; D055765:Shc Signaling Adaptor Proteins; C528035:Shc1 protein, rat; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; C552089:fibroblast receptor substrate 2, rat; D016220:Fibroblast Growth Factor 1; D014443:Tyrosine; D051966:Phospholipase C gamma