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.
Pei
Z
Z
School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Maloney
J A
JA
Yang
L
L
Williamson
J R
JR
D048868:Adaptor Proteins, Signal Transducing; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001152:Arsenicals / Q000494:pharmacology; D001665:Binding Sites; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism*; D051380:GRB2 Adaptor Protein; D007163:Immunosorbent Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051966:Phospholipase C gamma; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D001152:Arsenicals; D004791:Enzyme Inhibitors; D051380:GRB2 Adaptor Protein; C495950:Grb2 protein, rat; D007527:Isoenzymes; D011506:Proteins; D011993:Recombinant Fusion Proteins; D013438:Sulfhydryl Compounds; C029341:oxophenylarsine; D000804:Angiotensin II; D014443:Tyrosine; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma