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

The Journal of Biological Chemistry
Ziqiu WangB I Carr

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.

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Citations

Oct 18, 2002·Journal of Cellular Physiology·Brian I CarrSiddhartha Kar
Feb 13, 2003·Journal of Molecular Biology·Brian I CarrJohn S Lazo
May 21, 2013·Analytical Chemistry·Ryan M PhillipsNancy L Allbritton
Apr 12, 2005·Annual Review of Pharmacology and Toxicology·Alexander P DucruetJohn S Lazo
Jun 8, 2013·Cancer Discovery·Maria Teresa Herrera-AbreuNicholas C Turner
Nov 30, 2007·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Ziqiu WangBrian I Carr
Sep 17, 2008·International Journal of Cancer. Journal International Du Cancer·Susmita GhoshChinmay Kumar Panda
Jun 12, 2013·Molecular Systems Biology·Bertram KlingerNils Blüthgen
Jan 18, 2005·Biochemical and Biophysical Research Communications·Ira MelchheierLars-Oliver Klotz
Oct 23, 2004·Biochemical Pharmacology·Tetsuya OguriJohn S Lazo
Jan 7, 2015·Cell Cycle·Yann ThomasVéronique Baldin
May 26, 2015·Nature Cell Biology·Philippe DepeilleJeroen P Roose
Sep 17, 2016·Journal of Food Science·Xuelian JingLiping Zhang
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Apr 14, 2005·Molecular Cancer Therapeutics·Vincent P PeyregneBrian I Carr
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