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Publication : Requirement of JIP1-mediated c-Jun N-terminal kinase activation for obesity-induced insulin resistance.

First Author  Morel C Year  2010
Journal  Mol Cell Biol Volume  30
Issue  19 Pages  4616-25
PubMed ID  20679483 Mgi Jnum  J:163808
Mgi Id  MGI:4829819 Doi  10.1128/MCB.00585-10
Citation  Morel C, et al. (2010) Requirement of JIP1-Mediated c-Jun N-Terminal Kinase Activation for Obesity-Induced Insulin Resistance. Mol Cell Biol 30(19):4616-25
abstractText  The c-Jun NH(2)-terminal kinase (JNK) interacting protein 1 (JIP1) has been proposed to act as a scaffold protein that mediates JNK activation. However, recent studies have implicated JIP1 in multiple biochemical processes. Physiological roles of JIP1 that are related to the JNK scaffold function of JIP1 are therefore unclear. To test the role of JIP1 in JNK activation, we created mice with a germ line point mutation in the Jip1 gene (Thr(103) replaced with Ala) that selectively blocks JIP1-mediated JNK activation. These mutant mice exhibit a severe defect in JNK activation caused by feeding of a high-fat diet. The loss of JIP1-mediated JNK activation protected the mutant mice against obesity-induced insulin resistance. We conclude that JIP1-mediated JNK activation plays a critical role in metabolic stress regulation of the JNK signaling pathway.
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