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J. Biol. Chem., Vol. 278, Issue 12, 10731-10736, March 21, 2003
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From the The c-Jun N-terminal kinase (JNK) group of
mitogen-activated protein kinases (MAPKs) are activated by
pleiotropic signals including environmental stresses, growth factors,
and hormones. A subset of JNK can bind to distinct scaffold
proteins that also bind upstream kinases of the JNK pathway, allowing
sequential kinase activation within a signaling module. The
JNK-interacting protein-1 (JIP-1) scaffold protein specifically binds
JNK, MAP kinase kinase 7, and members of the MLK family and is
essential for stress-mediated JNK activation in neurones. Here we
report that JIP-1 also binds the dual-specificity phosphatases MKP7 and M3/6 via a region independent of its JNK binding domain. The
C-terminal region of MKP7, homologous to that of M3/6 but not other
DSPs, is required for interaction with JIP-1. When MKP7 is bound to JIP-1 it reduces JNK activation leading to reduced phosphorylation of
the JNK target c-Jun. These results indicate that the JIP-1 scaffold protein modulates JNK signaling via association with both
protein kinases and protein phosphatases that target JNK.
The JNK-interacting Protein-1 Scaffold Protein Targets
MAPK Phosphatase-7 to Dephosphorylate JNK*
§,§,, and
**
Department of Immunology and Molecular
Pathology, University College London and Royal Free Medical School,
Windeyer Institute, London W1T 4JF, United Kingdom and the
¶ School of Biological Sciences, University of Manchester, 2.205 Stopford Building, Oxford Road, Manchester M13 9PT, United Kingdom
*
This work was supported by the Association for International
Cancer Research, the Wellcome Trust, and Cancer Research UK.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
A Lister Institute-Jenner Research Fellow.
**
To whom correspondence should be addressed. Tel.: 44-161-275-7825;
Fax: 44-161-275-5082; E-mail: alan.j.whitmarsh@man.ac.uk.
Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
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