Peptide substrate recognition by the epidermal growth factor receptor

Cheryl A. Guyer, Randall L. Woltjer, Kenneth J. Coker, James V. Staros

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


The epidermal growth factor (EGF) receptor, like other protein tyrosine kinases, shows a preference for substrates having acidic residues in the vicinity of the tyrosyl residue that undergoes phosphorylation. We have developed a peptide substrate for the EGF receptor, termed tyrsub, which is based upon the highly acidic amino terminal sequence of human erythrocyte Band 3. Tyrsub possesses the lowest apparent Km(Km(app) = 32 μM) for phosphorylation by the EGF receptor of any peptide substrate reported to date. Using tyrsub, as well as analogs containing either Ser (sersub) or Phe (phesub) in place of Tyr, we investigated the relative importance of characteristics of the hydroxyaminoacyl residue in substrate recognition. Sersub was unable either to act as a substrate or serve as an effective inhibitor of tyrsub phosphorylation by the EGF receptor. Phesub was also unable to inhibit EGF-stimicrolable tyrsub phosphorylation, suggesting that the phenolic hydroxyl of the tyrosyl residue, rather than the aromatic ring, predominates in substrate recognition. These results indicate that for peptide substrates, at least, binding consists of two steps, recognition, in which the tyrosyl side chain plays the central role, and docking, in which residues surrounding the tyrosyl residue contribute to stabilizing binding interactions.

Original languageEnglish (US)
Pages (from-to)573-578
Number of pages6
JournalArchives of Biochemistry and Biophysics
Issue number2
StatePublished - Aug 1994
Externally publishedYes


  • EGF receptor
  • EGF receptor kinase
  • Epidermal growth factor
  • High affinity
  • Kinase
  • Kinetics
  • Peptide substrate
  • Peptide substrate
  • Phosphorylation
  • Protein tyrosine kinase
  • Receptor
  • Tyrosyl residues

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology


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