Negative feedback regulation of ASK1 by protein phosphatase 5 (PP5) in response to oxidative stress

被引：250

作者：

Morita, K ^{[1
]}

Saitoh, M ^{[1
]}

Tobiume, K ^{[1
]}

Matsuura, H ^{[1
]}

Enomoto, S ^{[1
]}

Nishitoh, H ^{[1
]}

Ichijo, H ^{[1
]}

机构：

[1] Tokyo Med & Dent Univ, Grad Sch, Bunkyo Ku, Tokyo 1138549, Japan

来源：

EMBO JOURNAL | 2001年 / 20卷 / 21期

关键词：

apoptosis; ASK1; MAP kinase; oxidative stress; PP5;

D O I：

10.1093/emboj/20.21.6028

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Apoptosis signal-regulating kinase 1 (ASK1) is a MAP kinase kinase kinase (MAPKKK) that activates the JNK and p38 MAP kinase cascades and is activated in response to oxidative stress such as hydrogen peroxide (H2O2). A yeast two-hybrid screening identified a serine/threonine protein phosphatase 5 (PP5) as a binding partner of ASK1. PP5 directly dephosphorylated an essential phospho-threonine residue within the kinase domain of ASK1 and thereby inactivated ASK1 activity in vitroandin vivo. The interaction between PP5 and ASK1 was induced by H2O2 treatment and was followed by the decrease in ASK1 activity. PP5 inhibited not only H2O2-induced sustained activation of ASK1 but also ASK1-dependent apoptosis. Thus, PP5 appears to act as a physiological inhibitor of ASK1-JNK/p38 pathways by negative feedback.

引用

页码：6028 / 6036

页数：9

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