Structural basis of interactions between epidermal growth factor receptor and SH2 domain proteins

Susan L. Sierke, G. Matthew Longo, John G. Koland

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

The structural basis of the interactions between the activated epidermal growth factor (EGF) receptor and SH2 domain proteins was investigated. The c-src SH2 domain (second domain of src homology) was expressed as a recombinant fusion protein, and an in vitro assay was developed to monitor EGF receptor/SH2 domain interactions. EGF receptor tyrosine kinase domain (TKD) forms expressed in the baculovirus/insect cell system were shown to bind to the SH2 domain when phosphorylated. These TKD/SH2 domain interactions were characterized by dissociation constants of 60-320 nM. Deletion analysis indicated that the entire SH2 domain was required for recognition of the phosphorylated TKD. The binding of a highly truncated TKD protein to the SH2 domain suggested that the sites recognized by the SH2 domain included the EGF receptor autophosphorylation site, tyr992. A phosphorylated EGF receptor peptide containing tyr992 was also shown to interact with the SH2 domain. This residue may therefore mediate interactions between the EGF receptor and tyrosine kinases in the src family.

Original languageEnglish (US)
Pages (from-to)45-54
Number of pages10
JournalBiochemical and Biophysical Research Communications
Volume191
Issue number1
DOIs
StatePublished - Feb 26 1993

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Structural basis of interactions between epidermal growth factor receptor and SH2 domain proteins'. Together they form a unique fingerprint.

Cite this