Negative regulation of MEKK1-induced signaling by glutathione S-transferase Mu

Kanghyun Ryoo, Sung H. Huh, Hee Lee Yong, Wan Yoon Kyoung, Ssang G. Cho, Eui Ju Choi

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 1 (MEKK1) is an important component in the stress-activated protein kinase pathway. Glutathione S-transferase Mu 1-1 (GST M1-1) has now been shown to inhibit the stimulation of MEKK1 activity induced by cellular stresses such as UV and hydrogen peroxide. GST M1-1 inhibited MEKK1 activation in a manner independent of its glutathione-conjugating catalytic activity. In vitro binding and kinase assays revealed that GST M1-1 directly bound MEKK1 and inhibited its kinase activity. Co-immunoprecipitation analysis showed a physical association between endogenous GST M1-1 and endogenous MEKK1 in L929 cells. Overexpressed GST M1-1 interfered with the binding of MEKK1 to SEK1 in transfected HEK293 cells. Furthermore, GST M1-1 suppressed MEKK1-mediated apoptosis. Taken together, our results suggest that GST M1-1 functions as a negative regulator of MEKK1.

Original languageEnglish
Pages (from-to)43589-43594
Number of pages6
JournalJournal of Biological Chemistry
Volume279
Issue number42
DOIs
Publication statusPublished - 2004 Oct 15

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Glutathione Transferase
Phosphotransferases
Extracellular Signal-Regulated MAP Kinases
Mitogen-Activated Protein Kinases
Protein Kinases
Hydrogen Peroxide
Glutathione
Assays
Catalyst activity
Chemical activation
Association reactions
Apoptosis
HEK293 Cells
Heat-Shock Proteins
Immunoprecipitation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Negative regulation of MEKK1-induced signaling by glutathione S-transferase Mu. / Ryoo, Kanghyun; Huh, Sung H.; Yong, Hee Lee; Kyoung, Wan Yoon; Cho, Ssang G.; Choi, Eui Ju.

In: Journal of Biological Chemistry, Vol. 279, No. 42, 15.10.2004, p. 43589-43594.

Research output: Contribution to journalArticle

Ryoo, Kanghyun ; Huh, Sung H. ; Yong, Hee Lee ; Kyoung, Wan Yoon ; Cho, Ssang G. ; Choi, Eui Ju. / Negative regulation of MEKK1-induced signaling by glutathione S-transferase Mu. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 42. pp. 43589-43594.
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