Glutathione-S-transferase as a selective inhibitor of oncogenic ras-p21- induced mitogenic signaling through blockade of activation of jun by jun-N- terminal kinase

Artjohn Villafania, Kamran Anwar, Shazia Amar, Lyndon Chie, Denise Way, Denise L. Chung, Victor Adler, Zeev Ronai, Paul W. Brandt-Rauf, Ziro Yamaizumii, Hsiang Fu Kung, Matthew R. Pincus

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

We have identified the intracellular detoxification enzyme, glutathione- S-transferase (GST), as a potent inhibitor of the activation of jun by its kinase, jun-N-terminal kinase (JNK), in vitro. All three major isozymes (α, μ, and π) bind to JNK-jun complexes and inhibit activation of jun by JNK. We now find that GST inhibits JNK-induced oocyte maturation in vivo and strongly inhibits oocyte maturation induced by oncogenic ras-p21 protein, but not by insulin-activated normal cellular p21 protein. These results correlate with the finding that oncogenic, but not insulin-activated normal, p21 induces high levels of activated JNK. GST also strongly blocks induction of oocyte maturation by protein kinase C (PKC) which is a critical downstream target of oncogenic but not normal ras-p21. Thus, we have established a new function for GST as a potent physiological inhibitor of the ras-JNK-jun pathway.

Original languageEnglish
Pages (from-to)57-64
Number of pages8
JournalAnnals of Clinical and Laboratory Science
Volume30
Issue number1
StatePublished - Jan 2000

Keywords

  • Glutathione-S-transferase
  • Oocyte maturation
  • Protein kinase C
  • jun
  • jun kinase
  • ras-p21

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