c-Src phosphorylates epidermal growth factor receptor on tyrosine 845

Biochem Biophys Res Commun. 1995 Oct 24;215(3):1078-87. doi: 10.1006/bbrc.1995.2574.


In the previous study [Sato et al. (1995) Biochem. Biophys. Res. Commun. 210, 844-851], we found that c-Src was associated with epidermal growth factor (EGF) receptor and activated upon EGF treatment in A431 cells. In the present study, we investigated the phosphorylation of EGF receptor by c-Src in the c-Src-EGF receptor complex. We have focused our attention to tyrosine residue 845 (Y845) of EGF receptor as a candidate for the phosphorylation site. A synthetic peptide containing Y845, named Y845 peptide, which corresponds to residue 837 to 856 of EGF receptor, was found to be phosphorylated by c-Src and used to provide the standard phosphopeptide. In addition to the autophosphorylated peptide of 25 kDa, a phosphopeptide of 7 kDa was detected in the cyanogen bromide-digested fragments of the c-Src-associated EGF receptor phosphorylated in vitro in an EGF-dependent manner. In phosphopeptide mapping, tryptic digest of the 7-kDa phosphopeptide was shown to co-migrate with that of the phosphorylated Y845 peptide. The 7-kDa phosphopeptide was found to be phosphorylated exclusively on tyrosine. These results suggest that c-Src can phosphorylate EGF receptor on Y845 in an EGF-dependent manner. Furthermore, we confirmed that the same site of the c-Src-associated EGF receptor was phosphorylated in EGF-treated A431 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Cyanogen Bromide
  • Epidermal Growth Factor / pharmacology*
  • ErbB Receptors / chemistry
  • ErbB Receptors / metabolism*
  • Humans
  • Mice
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Peptide Fragments / isolation & purification
  • Peptide Mapping
  • Phosphopeptides / chemistry
  • Phosphopeptides / isolation & purification
  • Phosphorylation
  • Phosphotyrosine / analysis
  • Proto-Oncogene Proteins pp60(c-src) / metabolism*
  • Substrate Specificity
  • Trypsin
  • Tyrosine*


  • Peptide Fragments
  • Phosphopeptides
  • Phosphotyrosine
  • Tyrosine
  • Epidermal Growth Factor
  • ErbB Receptors
  • Proto-Oncogene Proteins pp60(c-src)
  • Trypsin
  • Cyanogen Bromide