Is critically required for normal N-methyl-D-aspartic acid (NMDA) receptor function. This analysis led to the discovery that the JIP1/2 group of scaffold proteins That lack expression of both JIP1 and JIP2. To test the role of these scaffold proteins, we examined the phenotype of compound mutant mice JIP1 and JIP2 are structurally related scaffold proteins that share a similar tissue distribution, including high levels The analysis of additional phenotypes of JIP1-deficient mice may be compromised by partial compensation mediated by the scaffold 2003) and metabolic stress ( Jaeschke et al. Mice exhibit only a limited spectrum of defects, including the response to ischemia ( Whitmarsh et al. Together, these observations suggest that JIP1-deficient mice should have major physiological defects. 2001) and organelles, including mitochondria and synaptic vesicles ( Horiuchi et al. ProposedĬargoes are represented by the low-density lipoprotein receptor-related protein LRP8 ( Verhey et al. JIP1 may therefore influence the kinesin-mediated localization of cargo molecules and organelles within the cell.
Furthermore, JIP1 may also act as an adapter protein that links the kinesin-1 motor protein to cargoes ( Verhey et al. 2004).Īlthough JIP1 is established to be important for JNK regulation, it appears that JIP1 may also have other physiological functions.įor example, JIP1 is implicated in both the AKT and SRC signaling pathways ( Kim et al. 2003) and for JNK-mediated insulin resistance in type II diabetes ( Jaeschke et al. Thus, JIP1 is required for JNK activation and neuronal death in response to ischemia in vitro and stroke in vivo ( Whitmarsh et al. JNK activation ( Morrison and Davis 2003). Indeed, studies of JIP1-deficient mice confirm that this scaffold protein is essential for some forms of stress-induced That include the mitogen-activated protein (MAP) kinase kinase MKK7 and the mixed-lineage kinase group of MAP kinase kinase The JIP1 scaffold protein is implicated in the assembly and coordination of cJun N-terminal kinase (JNK) signaling modules We conclude that JIP scaffold proteins are critically required for normal Phosphorylation and activity of the NMDA receptor. JIP complexes interact with the SH2 domain of cFyn and may therefore promote tyrosine The decreased NMDA receptor activity in JIP-deficient neurons is associated with reduced tyrosine phosphorylation Mice were found to exhibit severe defects in N-methyl-D-aspartic acid (NMDA) receptor function, including decreased NMDA-evokedĬurrent amplitude, cytoplasmic Ca ++, and gene expression. Role of these scaffold proteins, we examined the phenotype of compound mutant mice that lack expression of JIP proteins. JIP scaffold proteins are implicated in the regulation of protein kinase signal transduction pathways.
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