title: A site of tyrosine phosphorylation in the C terminus of the epidermal growth factor receptor is required to activate phospholipase C.
abstract: Cells expressing mutant epidermal growth factor (EGF) receptors have been used to study mechanisms through which EGF increases phospholipase C (PLC) activity. C-terminal truncation mutant EGF receptors are markedly impaired in their ability to increase inositol phosphate formation compared with wild-type EGF receptors. Mutation of the single tyrosine self-phosphorylation site at residue 992 to phenylalanine in an EGF receptor truncated at residue 1000 abolished the ability of EGF to increase inositol phosphate formation. C-terminal deletion mutant receptors that are impaired in their ability to increase inositol phosphate formation effectively phosphorylate PLC-gamma at the same tyrosine residues as do wild-type EGF receptors. EGF enhances PLC-gamma association with wild-type EGF receptors but not with mutant receptors lacking sites of tyrosine phosphorylation. These results indicate that formation of a complex between self-phosphorylated EGF receptors and PLC-gamma is necessary for enzyme activation in vivo. We propose that both binding of PLC-gamma to activated EGF receptors and tyrosine phosphorylation of the enzyme are necessary to elicit biological responses. Kinase-active EGF receptors lacking sites of tyrosine phosphorylation are unable to signal increased inositol phosphate formation and increases in cytosolic Ca2+ concentration.
authors.affiliation: Department of Biology, School of Medicine, University of California, San Diego, La Jolla 92093-0650.
authors.forename: Q C
authors.initials: QC
authors.lastname: Vega
authors.forename: C
authors.initials: C
authors.lastname: Cochet
authors.forename: O
authors.initials: O
authors.lastname: Filhol
authors.forename: C P
authors.initials: CP
authors.lastname: Chang
authors.forename: S G
authors.initials: SG
authors.lastname: Rhee
authors.forename: G N
authors.initials: GN
authors.lastname: Gill
mesh_terms: D000818:Animals; D002460:Cell Line; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D009154:Mutation; D010766:Phosphorylation; D010738:Type C Phospholipases / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D007295:Inositol Phosphates; D014443:Tyrosine; D066246:ErbB Receptors; D010738:Type C Phospholipases