| We have been studying the regulation of protein kinases during the process of muscle atrophy or muscle wasting. The wasting of muscle occurs in response to low gravity conditions, extended bed rest or cancer (cachexia), however the molecular signals involved in this pathology are not well understood. Moreover, there are no current pharmacological treatments to prevent the development of muscle atrophy. Using a model of low gravity (hind-limb suspension) in collaboration with a group at NASA, we observed activation of the MAP kinases, an essential group of intracellular signaling enzymes. Specifically our studies pointed to the activation of c-Jun kinase (JNK), a kinase recently linked to phosphorylation of IRS-1 and the development of insulin resistance (3). Interestingly, we observed significantly enhanced phosphorylation and degradation of IRS-1 during the development of muscle atrophy. Therefore, the objectives of this project are to investigate the mechanisms by which JNK is activated during muscle atrophy and to determine the consequences of this event on muscle function. |