Document Detail

Identification of epidermal growth factor receptor as a target of Cdc25A protein phosphatase.
MedLine Citation:
PMID:  11912208     Owner:  NLM     Status:  MEDLINE    
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.
Ziqiu Wang; Meifang Wang; John S Lazo; Brian I Carr
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.     Date:  2002-03-23
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  277     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2002 May 
Date Detail:
Created Date:  2002-05-28     Completed Date:  2002-07-02     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  19470-5     Citation Subset:  IM    
Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
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MeSH Terms
3T3 Cells
Blotting, Western
Cell Division
Dose-Response Relationship, Drug
Fibroblasts / metabolism
Glutathione Transferase / metabolism
Growth Inhibitors / pharmacology
Precipitin Tests
Protein Binding
Protein Structure, Tertiary
Receptor, Epidermal Growth Factor / metabolism*
Signal Transduction
Time Factors
Tumor Cells, Cultured
Tyrosine / metabolism
Vitamin K / analogs & derivatives,  pharmacology
cdc25 Phosphatases / metabolism*
Grant Support
Reg. No./Substance:
0/2-(2-hydroxyethylsulfanyl)-3-methyl-1,4-naphthoquinone; 0/Growth Inhibitors; 12001-79-5/Vitamin K; 55520-40-6/Tyrosine; EC Transferase; EC, Epidermal Growth Factor; EC protein, mouse; EC protein, human; EC Phosphatases

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