Author： Jones D.A. Benjamin C.W.
Publisher： Elsevier
ISSN： 0003-9861
Source： Archives of Biochemistry and Biophysics, Vol.337, Iss.2, 1997-01, pp. : 143-148
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Abstract
Growth factor receptor binding protein-2 (GRB2) couples growth factor receptor activation to the p21-ras nucleotide exchange factor son-of-sevenless. Both GRB2 and son-of-sevenless display phosphorylation in cells treated with growth factors and may be subject to feed back regulation in mitogen-stimulated cells. Herein, we demonstrate that pp60 c- src can utilize GRB2 as a substrate. NIH 3T3 fibroblasts overexpressing pp60 v- src contained high levels of phosphorylated GRB2. In comparison, control fibroblasts contained phosphorylated GRB2 only after stimulation with platelet-derived growth factor. Analysis of GRB2 immune complexes isolated from fibroblasts stimulated with PDGF or transformed by pp60 v- src revealed a kinase activity capable of phosphorylating GRB2 in vitro. Incubation of native or recombinant GRB2 with purified pp60 c- src provided additional support for pp60 c- src as the kinase for GRB2. Deletion mutants of GRB2 demonstrated that pp60 c- src phosphorylated GRB2 on a tyrosine residue (residue 160) located between the SH2 domain and carboxyl terminal SH3 domain. Mutation of tyrosine 160 to phenylalanine abolished phosphorylation of GRB2 by pp60 c- src . We conclude that Src finds GRB2 a suitable substrate in vitro and may phosphorylate GRB2 in cells responding to platelet-derived growth factor.
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