Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3 Cells
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Animals
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Base Sequence
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Cell Line
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DNA Primers
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Fibroblast Growth Factor 1 / metabolism
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Fibroblast Growth Factor 1 / pharmacology*
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Isoenzymes / metabolism
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Mice
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Molecular Sequence Data
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Muscles
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Phosphorylation
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Phosphotyrosine
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Polymerase Chain Reaction
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Protein Serine-Threonine Kinases / metabolism
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Rats
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Receptor Protein-Tyrosine Kinases*
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Receptor, Fibroblast Growth Factor, Type 1
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Receptor, Fibroblast Growth Factor, Type 4
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Receptors, Fibroblast Growth Factor / biosynthesis
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Receptors, Fibroblast Growth Factor / drug effects
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Receptors, Fibroblast Growth Factor / physiology*
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Signal Transduction / drug effects
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Signal Transduction / physiology*
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Transfection
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Type C Phospholipases / metabolism
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Tyrosine / analogs & derivatives
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Tyrosine / analysis
Substances
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DNA Primers
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Isoenzymes
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Receptors, Fibroblast Growth Factor
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Fibroblast Growth Factor 1
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Phosphotyrosine
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Tyrosine
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Fgfr1 protein, mouse
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Fgfr1 protein, rat
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Fgfr4 protein, mouse
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Fgfr4 protein, rat
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Receptor Protein-Tyrosine Kinases
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Receptor, Fibroblast Growth Factor, Type 1
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Receptor, Fibroblast Growth Factor, Type 4
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Protein Serine-Threonine Kinases
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Calcium-Calmodulin-Dependent Protein Kinases
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Type C Phospholipases