Phosphoproteomics identified Endofin, DCBLD2, and KIAA0582 as novel tyrosine phosphorylation targets of EGF signaling and Iressa in human cancer cells

Yunhao Chen, Teck Yew Low, Lee Yee Choong, Rajarshi Sankar Ray, Yee Ling Tan, Weiyi Toy, Qingsong Lin, Keong Ang Boon, Hong Wong Chee, Simin Lim, Bin Li, Choy Leong Hew, Newman Siu Kwan Sze, Brian Druker, Yoon Pin Lim

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

With the completion of the human genome project, analysis of enriched phosphotyrosyl proteins from epidermal growth factor (EGF)-induced phosphotyrosine proteome permits the identification of novel downstream substrates of the EGF receptor (EGFR). Using cICAT-based LC-MS/MS method, we identified and relatively quantified the tyrosine phosphorylation levels of 21 proteins between control and EGF-treated A431 human cervical cancer cells. Of these, Endofin, DCBLD2, and KIAA0582 were validated to be novel tyrosine-phosphorylation targets of EGF signaling and Iressa, a highly selective inhibitor of EGFR. In addition, EGFR activity was shown to be necessary for EGF-induced localization of Endofin, an FYVE domain-containing protein regulated by phosphoinositol lipid and engaged in endosome-mediated receptor modulation. Although several groups have conducted phosphoproteomics of EGF signaling in recent years, our study is the first to identify and validate Endofin, DCBLD2, and KIAA0582 as part of a complex EGF phosphotyrosine signaling network. These novel data will provide new insights into the complex EGF signaling and may have implications on target-directed cancer therapeutics.

Original languageEnglish (US)
Pages (from-to)2384-2397
Number of pages14
JournalProteomics
Volume7
Issue number14
DOIs
Publication statusPublished - Jul 2007

    Fingerprint

Keywords

  • cICAT
  • DCBLD2
  • EGF
  • Endofin
  • Iressa

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

Cite this