Signal transduction by fibroblast growth factor receptor-4 (FGFR-4). Comparison with FGFR-1.
We have studied the signal transduction pathways of fibroblast growth factor receptor-4 (FGFR-4) and FGFR-1, which showed virtually identical acidic fibroblast growth factor binding profiles as well as tyrosine autophosphorylation upon activation in transfected L6 rat myoblasts and NIH3T3 mouse fibroblasts. A prominently tyrosyl-phosphorylated doublet of polypeptides of 85 kDa coprecipitated with activated FGFR-4 from both cell lines studied, but these polypeptides were not detected upon immunoprecipitation of activated FGFR-1. Furthermore, FGFR-4 induced only a weak tyrosyl phosphorylation of phospholipase C-gamma and no detectable tyrosyl phosphorylation of the SHC adaptor proteins in contrast to FGFR-1. No phosphorylation of Ras GTPase-activating protein, p64 Syp/PTP1D tyrosine phosphatase, or association of the GRB2 adaptor protein SH2 domain with these receptors was detected. Unlike FGFR-1, FGFR-4 induced only a barely detectable phosphorylation of the cellular serine/threonine kinase Raf-1 and a weaker tyrosyl phosphorylation of mitogen-activated protein kinases than FGFR-1. Despite these differences, stimulation of both receptors resulted in increased DNA synthesis.
Vainikka
S
S
Department of Pathology, University of Helsinki, Finland.
Joukov
V
V
Wennström
S
S
Bergman
M
M
Pelicci
P G
PG
Alitalo
K
K
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002460:Cell Line; D017931:DNA Primers; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009132:Muscles; D010766:Phosphorylation; D019000:Phosphotyrosine; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051499:Receptor, Fibroblast Growth Factor, Type 4; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014162:Transfection; D010738:Type C Phospholipases / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
D017931:DNA Primers; D007527:Isoenzymes; D017468:Receptors, Fibroblast Growth Factor; D016220:Fibroblast Growth Factor 1; D019000:Phosphotyrosine; D014443:Tyrosine; C496349:Fgfr1 protein, mouse; C496350:Fgfr1 protein, rat; C496372:Fgfr4 protein, mouse; C496373:Fgfr4 protein, rat; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051499:Receptor, Fibroblast Growth Factor, Type 4; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010738:Type C Phospholipases