An essential role of the JIP1 scaffold protein for JNK activation in adipose tissue.
The c-Jun NH2-terminal kinase (JNK) is activated during obesity. One consequence of obesity is that JNK phosphorylates the adapter protein insulin receptor substrate 1 (IRS-1) on Ser 307 and inhibits signaling by the insulin receptor. JNK can therefore cause peripheral insulin resistance during obesity and may contribute to the development of type 2 diabetes. Here we report that the JNK-interacting protein 1 (JIP1) scaffold protein, which binds components of the JNK signaling module, is essential for JNK activation in the adipose tissue of obese mice. These data identify JIP1 as a novel molecular target for therapeutic intervention in the development of obesity.
Howard Hughes Medical Institute and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester 01605, USA.
Anja
A
Jaeschke
Michael P
MP
Czech
Roger J
RJ
Davis
D048868:Adaptor Proteins, Signal Transducing; D000273:Adipose Tissue / Q000201:enzymology*; D000818:Animals; D004032:Diet; D004789:Enzyme Activation; D007333:Insulin Resistance; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D051379:Mice; D008810:Mice, Inbred C57BL; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C490665:Mapk8ip protein, mouse; D009687:Nuclear Proteins; D015534:Trans-Activators; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases