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Genes & Dev. 15 (18): 2421-2432

Copyright © 2001 by Cold Spring Harbor Laboratory Press.

Vol. 15, No. 18, pp. 2421-2432, September 15, 2001

Requirement of the JIP1 scaffold protein for stress-induced JNK activation

Alan J. Whitmarsh,1,6,8 Chia-Yi Kuan,4,7,8 Norman J. Kennedy,1,8 Nyaya Kelkar,1,8 Tarik F. Haydar,4 John P. Mordes,2 Michael Appel,2 Aldo A. Rossini,2 Stephen N. Jones,3 Richard A. Flavell,5 Pasko Rakic,4 and Roger J. Davis1,9

1 Howard Hughes Medical Institute and Program in Molecular Medicine, 2 Program in Molecular Medicine and Division of Diabetes, Department of Medicine, and 3 Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA; 4 Section of Neurobiology and 5 Howard Hughes Medical Institute and Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA

The c-Jun N-terminal kinase (JNK) signal transduction pathway is activated in response to the exposure of cells to environmental stress. Components of the JNK signaling pathway interact with the JIP1 scaffold protein. JIP1 is located in the neurites of primary hippocampal neurons. However, in response to stress, JIP1 accumulates in the soma together with activated JNK and phosphorylated c-Jun. Disruption of the Jip1 gene in mice by homologous recombination prevented JNK activation caused by exposure to excitotoxic stress and anoxic stress in vivo and in vitro. These data show that the JIP1 scaffold protein is a critical component of a MAP-kinase signal transduction pathway.

[Key Words: MAP kinase; scaffold; JIP1; JNK]

Present addresses: 6School of Biological Sciences, University of Manchester, Manchester, UK; 7Division of Developmental Biology, Cincinnati Children's Hospital Research Foundation, Cincinnati, OH 45229, USA.

8 These authors contributed equally to this work.

9 Corresponding author.

GENES & DEVELOPMENT 15:2421-2432 © 2001 by Cold Spring Harbor Laboratory Press  ISSN 0890-9369/01 $5.00

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