title: Serine 1002 is a site of in vivo and in vitro phosphorylation of the epidermal growth factor receptor.
abstract: 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, p34cdc2 was identified as a kinase capable of phosphorylating this serine residue. Purified Xenopus p34cdc2 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 p34cdc2 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.
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Missouri 63110.
authors.forename: D
authors.initials: D
authors.lastname: Kuppuswamy
authors.forename: M
authors.initials: M
authors.lastname: Dalton
authors.forename: L J
authors.initials: LJ
authors.lastname: Pike
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D066246:ErbB Receptors / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009865:Oocytes / Q000201:enzymology; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D010449:Peptide Mapping; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000378:metabolism; D014357:Trypsin / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014981:Xenopus
chemical_list: D010446:Peptide Fragments; D010768:Phosphoserine; D066246:ErbB Receptors; D016203:CDC2 Protein Kinase; D012697:Serine Endopeptidases; C028344:glutamyl endopeptidase; D014357:Trypsin