Molecular basis of distinct interactions between Dok1 PTB domain and tyrosine-phosphorylated EGF receptor

Yong Zhang, Zhiyong Yan, Amjad Farooq, Xiujie Liu, Changlin Lu, Ming Ming Zhou, Cheng He

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Phosphotyrosine binding (PTB) domains of the adaptor proteins Doks (downstream of tyrosine kinases) play an important role in regulating signal transduction of cell-surface receptors in cell growth, proliferation and differentiation; however, ligand specificity of the Dok PTB domains has until now remained elusive. In this study, we have investigated the molecular basis of specific association between the Dok1 PTB domain and the tyrosine- phosphorylated EGFR. Using yeast two-hybrid and biochemical binding assays, we show that only the PTB domain from Dok1 but not Dok4 or Dok5 can selectively bind to two known tyrosine phosphorylation sites at Y1086 and Y1148 in EGFR. Our structure-based mutational analyses define the molecular determinants for the two distinct Dok1 PTB domain/EGFR interactions and provide the structural understanding of the specific interactions between EGFR and PTB domains in the divergent Dok homologues.

Original languageEnglish
Pages (from-to)1147-1155
Number of pages9
JournalJournal of Molecular Biology
Volume343
Issue number4
DOIs
StatePublished - Oct 29 2004
Externally publishedYes

Fingerprint

Phosphotyrosine
Epidermal Growth Factor Receptor
Tyrosine
Cell Surface Receptors
Protein-Tyrosine Kinases
Cell Differentiation
Signal Transduction
Yeasts
Phosphorylation
Cell Proliferation
Ligands
Growth

Keywords

  • Dok1
  • EGF receptor
  • phosphotyrosine domain
  • tyrosine phosphorylation
  • yeast two-hybrid

ASJC Scopus subject areas

  • Virology

Cite this

Molecular basis of distinct interactions between Dok1 PTB domain and tyrosine-phosphorylated EGF receptor. / Zhang, Yong; Yan, Zhiyong; Farooq, Amjad; Liu, Xiujie; Lu, Changlin; Zhou, Ming Ming; He, Cheng.

In: Journal of Molecular Biology, Vol. 343, No. 4, 29.10.2004, p. 1147-1155.

Research output: Contribution to journalArticle

Zhang, Yong ; Yan, Zhiyong ; Farooq, Amjad ; Liu, Xiujie ; Lu, Changlin ; Zhou, Ming Ming ; He, Cheng. / Molecular basis of distinct interactions between Dok1 PTB domain and tyrosine-phosphorylated EGF receptor. In: Journal of Molecular Biology. 2004 ; Vol. 343, No. 4. pp. 1147-1155.
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