Requirement of the JIP1 scaffold protein for stress-induced JNK activation.
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.
Whitmarsh
A J
AJ
Howard Hughes Medical Institute and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Kuan
C Y
CY
Kennedy
N J
NJ
Kelkar
N
N
Haydar
T F
TF
Mordes
J P
JP
Appel
M
M
Rossini
A A
AA
Jones
S N
SN
Flavell
R A
RA
Rakic
P
P
Davis
R J
RJ
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004789:Enzyme Activation / Q000502:physiology; D048031:JNK Mitogen-Activated Protein Kinases; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009474:Neurons / Q000201:enzymology / Q000378:metabolism; D018384:Oxidative Stress
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C490665:Mapk8ip protein, mouse; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases