Identification of epidermal growth factor receptor as a target of Cdc25A protein phosphatase

Ziqiu Wang, Meifang Wang, John S. Lazo, Brian I. Carr

Research output: Contribution to journalArticle

Abstract

Cdc25A, a dual-specificity protein phosphatase, plays a critical role in cell cycle progression. Although cyclin-dependent kinases are established substrates, Cdc25A may also affect other proteins. We have shown here that Cdc25A interacts with epidermal growth factor receptor (EGFR) both physically and functionally in Hep3B human hepatoma cells. Cdc25A inhibitor Cpd 5, a vitamin K analog, inhibited Cdc25A activity in the Cdc25A-EGFR immunocomplex and consequently caused prolonged EGFR tyrosine phosphorylation. Both purified GST-Cdc25A protein and endogenous Hep3B cellular Cdc25A dephosphorylated tyrosine-phosphorylated EGFR, and Cpd 5 antagonized the phosphatase activity of Cdc25A. A functional Cdc25A-EGFR interaction was seen in NR-6 fibroblasts expressing ectopic EGFR but not with a receptor lacking the C terminus or a mutated kinase domain. These data link the cell cycle control Cdc25A phosphatase to an EGFR-linked mitogenic signaling pathway specifically involving EGFR dephosphorylation.

Original languageEnglish
Pages (from-to)19470-19475
Number of pages6
JournalJournal of Biological Chemistry
Volume277
Issue number22
DOIs
Publication statusPublished - May 31 2002

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ASJC Scopus subject areas

  • Biochemistry

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