The c-Jun N-terminal kinase (INK) signal transduction pathway is activated
in response to the exposure of cells to environmental stress. Components of
the INK signaling pathway interact with the JIP1 scaffold protein. JIP1 is
located in the neurites of primary hippocampal neurons. However, in respon
se to stress, JIP1 accumulates in the soma together with activated JNK and
phosphorylated c-Jun. Disruption of the jip1 gene in mice by homologous rec
ombination prevented JNK activation caused by exposure to excitotoxic stres
s and anoxic stress in vivo and in vitro. These data show that the JIP1 sca
ffold protein is a critical component of a MAP-kinase signal transduction p
athway.