Inhibition of hGrb10 binding to the insulin receptor by functional domain-mediated oligomerization

Lily Q. Dong, Sarah Porter, Derong Hu, Feng Liu

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


hGrb10 is a newly identified Src homology 2 (SH2) and pleckstrin homology (PH) domain-containing protein that binds to autophosphorylated receptor tyrosine kinases, including the insulin and insulin-like growth factor receptors. To identify potential downstream proteins that interact with hGrb10, we screened a yeast two-hybrid cDNA library using the full- length hGrb10γ as bait. A fragment of hGrb10, which included the IPS (insert between the PH and SH2 domain) and the SH2 domains, was found to bind with high affinity to the full-length protein. The interaction between the IPS/SH2 domain and the full-length hGrb10 was further confirmed by in vitro glutathione S-transferase fusion protein binding studies. Gel filtration assays showed that hGrb10 underwent tetramerization in mammalian cells. The interaction involved at least two functional domains, the IPS/SH2 region and the PH domain, both of which interacted with the NH2-terminal amino acid sequence of hGrb10γ (hGrb10γΔC, residues 4-414). Competition studies showed that hGrb10γΔC inhibited the binding of hGrb10 to the tyrosine- phosphorylated insulin receptor, suggesting that this region may play a regulatory role in hGrb10/insulin receptor interaction. We present a model for hGrb10 tetramerization and its potential role in receptor tyrosine kinase signal transduction.

Original languageEnglish (US)
Pages (from-to)17720-17725
Number of pages6
JournalJournal of Biological Chemistry
Issue number28
StatePublished - Jul 10 1998

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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