Serine 1002 is a site of in vivo and in vitro phosphorylation of the epidermal growth factor receptor

We have shown previously that treatment of A431 cells with epidermal growth factor (EGF) induces desensitization of the EGF receptor. We now show that this desensitization is associated with an increase in the phosphorylation of the receptor on Ser-1002. Using a synthetic peptide corresponding to the sequence surrounding Ser-1002, p34^cdc2 was identified as a kinase capable of phosphorylating this serine residue. Purified Xenopus p34^cdc2 was found to phosphorylate the synthetic peptide on the serine residue corresponding to Ser-1002. This kinase also phosphorylated purified EGF receptor in vitro on Ser-1002. Phosphorylation of the EGF receptor by p34^cdc2 was associated with a decrease in its tyrosine protein kinase activity. These data indicate that the EGF receptor may be a target for phosphorylation by a cyclin-dependent kinase in vivo and imply that receptor function may be regulated in a cell cycle-dependent fashion.