Novel recognition motif on fibroblast growth factor receptor mediates direct association and activation of SNT adapter proteins.
Fibroblast growth factors (FGFs) stimulate tyrosine phosphorylation of a membrane-anchored adapter protein, FRS2/SNT-1, promoting its association with Shp-2 tyrosine phosphatase and upstream activators of Ras. Using the yeast two-hybrid protein-protein interaction assay, we show that FRS2/SNT-1 and a newly isolated SNT-2 protein directly bind to FGF receptor-1 (FGFR-1). A juxtamembrane ... segment of FGFR-1 and the phosphotyrosine-binding domain of SNTs are both necessary and sufficient for interaction in yeast and in vitro, and FGFR-mediated SNT tyrosine phosphorylation in vivo requires these segments of receptor and SNT. Our findings establish SNTs as direct protein links between FGFR-1 and multiple downstream pathways. The SNT binding motif of FGFR-1 is distinct from previously described phosphotyrosine-binding domain recognition motifs, lacking both tyrosine and asparagine residues.
Mesh Terms:
3T3 Cells, Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, Binding Sites, Carrier Proteins, Ligands, Lipoproteins, Membrane Proteins, Mice, Molecular Sequence Data, Molecular Weight, Phosphoproteins, Phosphorylation, Protein Binding, Receptor Protein-Tyrosine Kinases, Receptor, Fibroblast Growth Factor, Type 1, Receptors, Fibroblast Growth Factor, Tyrosine
3T3 Cells, Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, Binding Sites, Carrier Proteins, Ligands, Lipoproteins, Membrane Proteins, Mice, Molecular Sequence Data, Molecular Weight, Phosphoproteins, Phosphorylation, Protein Binding, Receptor Protein-Tyrosine Kinases, Receptor, Fibroblast Growth Factor, Type 1, Receptors, Fibroblast Growth Factor, Tyrosine
J. Biol. Chem.
Date: Jul. 17, 1998
PubMed ID: 9660748
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