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Epidermal growth factor-dependent phosphorylation of lipocortin

Abstract

Lipocortin-like proteins are a family of steroid-induced inhibitors of phospholipase activity with potential anti-inflammatory activity (for reviews see refs 1, 2). Related proteins have been detected in a variety of tissues and species3–7. The best characterized form is a protein of relative molecular mass (Mr)40,000 (40K), which is phosphorylated in vivo by protein tyrosine kinases and by protein serine-threonine kinases8,9. It has been proposed that the phospholipase inhibitory activity of lipocortin can be regulated by its phosphorylation5. In the A431 cell line, a protein of 35K is phosphorylated by the protein tyrosine kinase activity of the epidermal growth factor (EGF) receptor10. Here we report that human lipocortin is phosphorylated near its amino terminus by the EGF receptor/kinase. By peptide mapping and immunological analyses, we show that lipocortin and the endogenous 35K substrate for the EGF receptor/kinase from A431 cells are the same protein.

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