A site of tyrosine phosphorylation in the C terminus of the epidermal growth factor receptor is required to activate phospholipase C

Quinn Vega, C. Cochet, O. Filhol, C. P. Chang, Goo Rhee Sue Goo Rhee, G. N. Gill

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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-γ at the same tyrosine residues as do wild-type EGF receptors. EGF enhances PLC-γ 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-γ is necessary for enzyme activation in vivo. We propose that both binding of PLC-γ 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.

Original languageEnglish
Pages (from-to)128-135
Number of pages8
JournalMolecular and Cellular Biology
Volume12
Issue number1
DOIs
StatePublished - 1 Jan 1992

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Type C Phospholipases
Epidermal Growth Factor Receptor
Tyrosine
Phosphorylation
Inositol Phosphates
Epidermal Growth Factor
Enzyme Activation
ErbB Receptors
Phenylalanine
Mutation
Enzymes

Cite this

Vega, Quinn ; Cochet, C. ; Filhol, O. ; Chang, C. P. ; Sue Goo Rhee, Goo Rhee ; Gill, G. N. / A site of tyrosine phosphorylation in the C terminus of the epidermal growth factor receptor is required to activate phospholipase C. In: Molecular and Cellular Biology. 1992 ; Vol. 12, No. 1. pp. 128-135.
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A site of tyrosine phosphorylation in the C terminus of the epidermal growth factor receptor is required to activate phospholipase C. / Vega, Quinn; Cochet, C.; Filhol, O.; Chang, C. P.; Sue Goo Rhee, Goo Rhee; Gill, G. N.

In: Molecular and Cellular Biology, Vol. 12, No. 1, 01.01.1992, p. 128-135.

Research output: Contribution to journalArticleResearchpeer-review

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