Abstract
In response to fibroblast growth factor (FGF), FGF receptor-1 (FGFR-1) (flg) becomes tyrosine phosphorylated and associates with phospholipase C gamma (PLC gamma) and a 90 kDa protein. We report here that in cells transformed by v-Src, FGFR-1 becomes phosphorylated on tyrosine; however, neither PLC gamma nor p90 was found to be associated with tyrosine-phosphorylated FGFR-1. Instead, there was a strong constitutive association of FGFR-1 with the adaptor proteins Shc and Grb2 and the Ras guanine nucleotide exchange factor Sos. Association with Shc and Grb2 and Sos was not observed in response to FGF. Suramin did not prevent either tyrosine phosphorylation or Shc/Grb2/Sos association, indicating a non-autocrine mechanism. Thus, in cells transformed by v-Src, tyrosine phosphorylation of FGFR-1 results not in the expected association with PLC gamma and p90, but rather in the recruitment of the Ras activating Shc/Grb2/Sos complex. These data suggest a mechanism for Ras activation by v-Src involving phosphorylation of novel tyrosine(s) on FGFR-1.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3T3 Cells
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Adaptor Proteins, Signal Transducing*
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Adaptor Proteins, Vesicular Transport*
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Animals
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Fibroblast Growth Factors / pharmacology
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GRB2 Adaptor Protein
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Genes, src / genetics*
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Glucosidases
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Intracellular Signaling Peptides and Proteins*
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Isoenzymes / metabolism
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Membrane Proteins / metabolism*
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Mice
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Myristoylated Alanine-Rich C Kinase Substrate
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Phospholipase C gamma
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Phosphoproteins / metabolism
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Phosphotyrosine / analysis
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Phosphotyrosine / metabolism
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Proteins / metabolism*
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Receptor Protein-Tyrosine Kinases*
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Receptor, Fibroblast Growth Factor, Type 1
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Receptors, Fibroblast Growth Factor / metabolism*
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Shc Signaling Adaptor Proteins
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Signal Transduction / physiology
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Son of Sevenless Proteins
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Src Homology 2 Domain-Containing, Transforming Protein 1
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Suramin / pharmacology
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Transformation, Genetic / genetics*
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Type C Phospholipases / metabolism
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ras Proteins / physiology
Substances
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Adaptor Proteins, Signal Transducing
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Adaptor Proteins, Vesicular Transport
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GRB2 Adaptor Protein
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Grb2 protein, mouse
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Intracellular Signaling Peptides and Proteins
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Isoenzymes
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Membrane Proteins
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Phosphoproteins
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Prkcsh protein, mouse
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Proteins
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Receptors, Fibroblast Growth Factor
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Shc Signaling Adaptor Proteins
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Shc1 protein, mouse
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Son of Sevenless Proteins
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Src Homology 2 Domain-Containing, Transforming Protein 1
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Myristoylated Alanine-Rich C Kinase Substrate
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Phosphotyrosine
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Suramin
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Fibroblast Growth Factors
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Fgfr1 protein, mouse
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Receptor Protein-Tyrosine Kinases
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Receptor, Fibroblast Growth Factor, Type 1
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Type C Phospholipases
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Phospholipase C gamma
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Glucosidases
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ras Proteins