A new function for phospholipase C-gamma1: coupling to the adaptor protein GRB2.
Epidermal growth factor (EGF)-induced autophosphorylation of the EGF receptor results in high-affinity binding of the adaptor protein GRB2, which serves as a convergence point for multiple signaling pathways. Present studies demonstrate that EGF induces the co-immunoprecipitation of phospholipase C (PLC)-gamma1 with the adaptor protein GRB2 and the guanine nucleotide exchange ... factor Sos, but not with the adaptor protein SHC, in WB cells. Inhibition of PLC-gamma1 tyrosine phosphorylation by phenylarsine oxide reduces the co-immunoprecipitation of PLC-gamma1 with GRB2. Furthermore, angiotensin II, a G protein-coupled receptor agonist, also induces the tyrosine phosphorylation of PLC-gamma1 and its co-immunoprecipitation with GRB2 in WB cells. Interestingly, angiotensin II stimulation also causes tyrosine phosphorylation of the EGF receptor, suggesting that angiotensin II-induced PLC-gamma1 tyrosine phosphorylation in WB cells may be via EGF receptor tyrosine kinase activation. In addition, there is some level of association between PLC-gamma1 and GRB2 that is independent of the tyrosine phosphorylation of PLC-gamma1 in both in vivo and in vitro studies. In vitro studies further demonstrate that the Tyr771 and Tyr783 region of PLC-gamma1 and the SH2 domain of GRB2 are potentially involved in the tyrosine phosphorylation-dependent association between PLC-gamma1 and GRB2. The association of PLC-gamma1 with GRB2 and Sos suggests that PLC-gamma1 may be directly involved in the Ras signaling pathway and that GRB2 may be involved in the translocation of PLC-gamma1 from cytosol to the plasma membrane as a necessary step for its effect on inositol lipid hydrolysis.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Angiotensin II, Animals, Arsenicals, Binding Sites, Cell Line, Cricetinae, Cricetulus, Enzyme Inhibitors, Epidermal Growth Factor, GRB2 Adaptor Protein, Immunosorbent Techniques, Isoenzymes, Phospholipase C gamma, Phosphorylation, Protein-Tyrosine Kinases, Proteins, Rats, Receptor, Epidermal Growth Factor, Recombinant Fusion Proteins, Sulfhydryl Compounds, Type C Phospholipases, Tyrosine
Adaptor Proteins, Signal Transducing, Angiotensin II, Animals, Arsenicals, Binding Sites, Cell Line, Cricetinae, Cricetulus, Enzyme Inhibitors, Epidermal Growth Factor, GRB2 Adaptor Protein, Immunosorbent Techniques, Isoenzymes, Phospholipase C gamma, Phosphorylation, Protein-Tyrosine Kinases, Proteins, Rats, Receptor, Epidermal Growth Factor, Recombinant Fusion Proteins, Sulfhydryl Compounds, Type C Phospholipases, Tyrosine
Arch. Biochem. Biophys.
Date: Sep. 01, 1997
PubMed ID: 9281317
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