Requirement of the JIP1 scaffold protein for stress-induced JNK activation
- Alan J. Whitmarsh1,6,8,
- Chia-Yi Kuan4,7,8,
- Norman J. Kennedy1,8,
- Nyaya Kelkar1,8,
- Tarik F. Haydar4,
- John P. Mordes2,
- Michael Appel2,
- Aldo A. Rossini2,
- Stephen N. Jones3,
- Richard A. Flavell5,
- Pasko Rakic4, and
- Roger J. Davis1,9
- 1Howard Hughes Medical Institute and Program in Molecular Medicine, 2Program in Molecular Medicine and Division of Diabetes, Department of Medicine, and 3Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA; 4Section of Neurobiology and 5Howard Hughes Medical Institute and Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
Abstract
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 theJip1 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.
Keywords
Footnotes
-
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.
-
E-MAIL Roger.Davis{at}Umassmed.edu; FAX (508) 856-3210.
-
Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.922801.
-
- Received June 22, 2001.
- Accepted July 31, 2001.
- Cold Spring Harbor Laboratory Press
