TI - Epidermal growth factor receptor threonine and serine residues phosphorylated in vivo . AB - The epidermal growth factor ( EGF ) receptor is regulated by EGF -stimulated autophosphorylation and by phorbol ester -stimulated , protein kinase C ( Ca2+/phospholipid -dependent enzyme ) mediated phosphorylation at identified sites . The EGF receptor contains additional phosphorylation sites including a prominent phosphothreonine and several phosphoserines which account for the majority of phosphate covalently bound to the receptor in vivo . We have identified three of these sites in EGF receptor purified from 32P-labeled A431 cells . The major phosphothreonine was identified as threonine 669 in the EGF receptor sequence . Phosphoserine residues were identified as serines 671 and 1046/1047 of the EGF receptor . Two other phosphoserine residues were localized to tryptic peptides containing multiple serine residues located carboxyl terminal to the conserved protein kinase domain . The amino acid sequences surrounding the three identified phosphorylation sites are highly conserved in the EGF receptor and the protein products of the v-erb B and neu oncogenes . Analysis of predicted secondary structure of the EGF receptor reveals that all of the phosphorylation sites are located near beta turns . In A431 cells phosphorylation of the serine residues was dependent upon serum . In mouse B82 L cells transfected with a wild type human EGF receptor . EGF increased the 32P content in all tryptic phosphopeptides . A mutant EGF receptor lacking protein tyrosine kinase activity was phosphorylated only at threonine 669 . Regulated phosphorylation of the EGF receptor at these threonine and serine residues may influence aspects of receptor function .