title: Fibroblast growth factor receptors have different signaling and mitogenic potentials.
abstract: Fibroblast growth factor (FGF) receptors (FGFRs) are structurally related receptor protein tyrosine kinases encoded by four distinct genes. Activation of FGFR-1, -2, and -3 by FGFs induces mitogenic responses in various cell types, but the mitogenic potential of FGFR-4 has not been previously explored. We have compared the properties of BaF3 murine lymphoid cells and L6 rat myoblast cells engineered to express FGFR-1 or FGFR-4. Acidic FGF binds with high affinity to and elicits tyrosine phosphorylation of FGFR-1 or FGFR-4 receptors displayed on BaF3 cells, but only FGFR-1 activation leads to cell survival and growth. FGFR-4 activation also fails to elicit detectable signals characteristic of the FGFR-1 response: tyrosine phosphorylation of SHC and extracellular signal-related kinase (ERK) proteins and induction of fos and tis11 RNA expression. The only detected response to FGFR-4 activation was weak phosphorylation of phospholipase C gamma. A chimeric receptor containing the extracellular domain of FGFR-4 and the intracellular domain of FGFR-1 confers FGF-dependent growth upon transfected BaF3 cells, demonstrating that the intracellular domains of the receptors dictate their functional capacity. Activation of FGFR-1 in transfected L6 myoblasts induced far stronger phosphorylation of phospholipase C gamma, SHC, and ERK proteins than could activation of FGFR-4 in L6 cells, and only FGFR-1 activation induced tyrosine phosphorylation of a characteristic 80-kD protein. Hence, the signaling and biological responses elicited by different FGF receptors substantially differ.
authors.affiliation: Regeneron Pharmaceuticals, Inc., Tarrytown, New York 10591.
authors.forename: J K
authors.initials: JK
authors.lastname: Wang
authors.forename: G
authors.initials: G
authors.lastname: Gao
authors.forename: M
authors.initials: M
authors.lastname: Goldfarb
mesh_terms: D000818:Animals; D002417:Cattle; D002455:Cell Division / Q000502:physiology*; D002460:Cell Line; D003001:Cloning, Molecular; D015870:Gene Expression; D006801:Humans; D051379:Mice; D010766:Phosphorylation; D011817:Rabbits; D051381:Rats; D017468:Receptors, Fibroblast Growth Factor / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism
chemical_list: D017468:Receptors, Fibroblast Growth Factor; D011993:Recombinant Fusion Proteins; D014443:Tyrosine