Negative feedback regulation of ASK1 by protein phosphatase 5 (PP5) in response to oxidative stress
Open Access
- 1 November 2001
- journal article
- research article
- Published by Springer Nature in The EMBO Journal
- Vol. 20 (21) , 6028-6036
- https://doi.org/10.1093/emboj/20.21.6028
Abstract
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 vitro and in 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.Keywords
This publication has 57 references indexed in Scilit:
- From receptors to stress-activated MAP kinasesOncogene, 1999
- The tetratricopeptide repeat: a structural motif mediating protein-protein interactionsBioEssays, 1999
- MAPKKK6, a Novel Mitogen-Activated Protein Kinase Kinase Kinase, That Associates with MAPKKK5Biochemical and Biophysical Research Communications, 1998
- Molecular Cloning and Characterization of the Mouse Apoptosis Signal-Regulating Kinase 1Biochemical and Biophysical Research Communications, 1997
- Induction of Apoptosis by ASK1, a Mammalian MAPKKK That Activates SAPK/JNK and p38 Signaling PathwaysScience, 1997
- The Tetratricopeptide Repeat Domain of Protein Phosphatase 5 Mediates Binding to Glucocorticoid Receptor Heterocomplexes and Acts as a Dominant Negative MutantJournal of Biological Chemistry, 1996
- A member of the MAP kinase phosphatase gene family in mouse containing a complex trinucleotide repeat in the coding regionHuman Molecular Genetics, 1996
- Opposing Effects of ERK and JNK-p38 MAP Kinases on ApoptosisScience, 1995
- hVH‐5: A Protein Tyrosine Phosphatase Abundant in Brain that Inactivates Mitogen‐Activated Protein KinaseJournal of Neurochemistry, 1995
- The MAP kinase cascade is essential for diverse signal transduction pathwaysTrends in Biochemical Sciences, 1993