Abstract
STIMULATION of growth factor receptors with tyrosine kinase activity is followed by rapid receptor dimerization, tyrosine autophosphorylation and phosphorylation of signalling molecules such as phospholipase Cγ(PLCγ) and the ros GTPase-activating protein1,2. PLCγ and GTPase-activating protein bind to specific tyrosine-phosphorylated regions in growth factor receptors3–9through their sir-homologous SH2 domains7,8,10,11. Growth factor-induced tyrosine phosphorylation of PLCγ is essential for stimulation of phosphatidylinositol hydrolysis in vitro12 and in vivo13. We have shown that a short phosphorylated peptide containing tyrosine at position 766 from a conserved region14–18 of the fibre-blast growth factor (FGF) receptor is a binding site for the SH2 domain of PLCγ (ref. 8). Here we show that an FGF receptor point mutant in which Tyr766 is replaced by a phenylalanine residue (Y766F) is unable to associate with and tyrosine-phosphorylate PLCγ or to stimulate hydrolysis of phosphatidylinositol. Nevertheless, the Y766F FGF receptor mutant can be autophos-phorylated, and can phosphorylate several cellular proteins and stimulate DNA synthesis. Our data show that phosphorylation of the conserved Tyr 766 of the FGF receptor is essential for phosphorylation of PLCγ and for hydrolysis of phosphatidylinositol, but that elimination of this hydrolysis does not affect FGF-induced mitogenesis.
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Mohammadi, M., Dionne, C., Li, W. et al. Point mutation in FGF receptor eliminates phosphatidylinositol hydrolysis without affecting mitogenesis. Nature 358, 681–684 (1992). https://doi.org/10.1038/358681a0
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DOI: https://doi.org/10.1038/358681a0
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