Requirement of JIP scaffold proteins for NMDA-mediated signal transduction.
JIP scaffold proteins are implicated in the regulation of protein kinase signal transduction pathways. To test the physiological role of these scaffold proteins, we examined the phenotype of compound mutant mice that lack expression of JIP proteins. These mice were found to exhibit severe defects in N-methyl-D-aspartic acid (NMDA) receptor function, including decreased NMDA-evoked current amplitude, cytoplasmic Ca(++), and gene expression. The decreased NMDA receptor activity in JIP-deficient neurons is associated with reduced tyrosine phosphorylation of NR2 subunits of the NMDA receptor. JIP complexes interact with the SH2 domain of cFyn and may therefore promote tyrosine phosphorylation and activity of the NMDA receptor. We conclude that JIP scaffold proteins are critically required for normal NMDA receptor function.
Kennedy
Norman J
NJ
Howard Hughes Medical Institute and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Martin
Gilles
G
Ehrhardt
Anka G
AG
Cavanagh-Kyros
Julie
J
Kuan
Chia-Yi
CY
Rakic
Pasko
P
Flavell
Richard A
RA
Treistman
Steven N
SN
Davis
Roger J
RJ
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology*; D000818:Animals; D019556:COS Cells; D002531:Cerebellum / Q000196:embryology / Q000378:metabolism; D002522:Chlorocebus aethiops; D016547:Kinesins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016202:N-Methylaspartate / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; C490665:Mapk8ip protein, mouse; C486564:Mapk8ip2 protein, mouse; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D011505:Protein-Tyrosine Kinases; D016547:Kinesins