title: Phospholipase C-gamma 1 binding to intracellular receptors for activated protein kinase C.
abstract: Phospholipase C-gamma 1 (PLC-gamma 1; EC 3.1.4.11) hydrolyzes phosphatidylinositol 4,5-bisphosphate to generate diacylglycerol and inositol 1,4,5-trisphosphate and is activated in response to growth factor stimulation and tyrosine phosphorylation. Concomitantly, the enzyme translocates from the cytosol to the particulate cell fraction. A similar process of activation-induced translocation from the cytosol to the cell particulate fraction has also been described for protein kinase C (PKC). We have previously shown that activated PKC binds to specific receptor proteins, receptors for activated C kinase, or RACKs, of approximately 30 kDa. Here, we show that PLC-gamma 1 bound to these RACKs and inhibited subsequent PKC binding to RACKs. However, unlike PKC, the binding of PLC-gamma 1 to RACKs did not require phospholipids and calcium. After epidermal growth factor treatment of intact A-431 cells, the binding of PLC-gamma 1 to RACKs increased as compared with PLC-gamma 1 from control cells. This increase in PLC-gamma 1 binding to RACKs was due to the phosphorylation of PLC-gamma 1. Additional data indicated that PLC-gamma 1 binds to RACKs in solution; epidermal growth factor receptor-dependent PLC-gamma 1 phosphorylation and activation decreased in the presence of RACKs. It is possible that, in vivo, PLC-gamma 1 associates with RACKs or with other PLC-gamma 1-specific anchoring proteins in the particulate cell fraction. Since a PKC C2 homologous region is present in PLC-gamma 1, the C2 region may mediate the activation-induced translocation of the enzyme to the cell particulate fraction and the anchoring protein-PLC-gamma 1 complex may be the active translocated form of PLC-gamma 1.
authors.affiliation: Department of Molecular Pharmacology, School of Medicine, Stanford University, CA 94305-5332.
authors.forename: M H
authors.initials: MH
authors.lastname: Disatnik
authors.forename: S M
authors.initials: SM
authors.lastname: Hernandez-Sotomayor
authors.forename: G
authors.initials: G
authors.lastname: Jones
authors.forename: G
authors.initials: G
authors.lastname: Carpenter
authors.forename: D
authors.initials: D
authors.lastname: Mochly-Rosen
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D002460:Cell Line; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008969:Molecular Sequence Data; D051966:Phospholipase C gamma; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D010738:Type C Phospholipases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D007527:Isoenzymes; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D004815:Epidermal Growth Factor; D011493:Protein Kinase C; D010738:Type C Phospholipases; D051966:Phospholipase C gamma