UMMS Affiliation

Program in Molecular Medicine; Department of Medicine, Division of Endocrinology, Metabolism and Diabetes

Date

10-1-2010

Document Type

Article

Medical Subject Headings

Adaptor Proteins, Signal Transducing; Adipokines; Animals; Blood Glucose; Cytokines; Dietary Fats; Energy Metabolism; Enzyme Activation; Fatty Liver; Female; Immunoblotting; Insulin; *Insulin Resistance; JNK Mitogen-Activated Protein Kinases; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction

Disciplines

Biochemistry | Cell Biology | Cellular and Molecular Physiology | Molecular Biology

Abstract

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.

Rights and Permissions

Citation: Mol Cell Biol. 2010 Oct;30(19):4616-25. doi: 10.1128/MCB.00585-10. Epub 2010 Aug 2. Link to article on publisher's site

Comments

Publisher's PDF posted as allowed by the publisher's author rights policy at http://journals.asm.org/site/misc/ASM_Author_Statement.xhtml.

Related Resources

Link to Article in PubMed

PubMed ID

20679483

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