Mitogen-activated protein kinase phosphatase-1-a potential therapeutic target in metabolic disease

Importance of the field: Metabolic disease, which is associated with obesity and cardiovascular disease, is a worldwide epidemic. There continues to be a tremendous effort towards the development of therapies to curtail obesity and its associated pathophysiological sequelae. MAPKs have been implicated in metabolic disease suggesting that these enzymes, and those that regulate them, can potentially serve as therapeutic targets to combat this disease. The MAPK phosphatase-1 (MKP-1) mediates the dephosphorylation and inactivation of MAPKs in insulin-responsive tissues. Therefore, the actions of MKP-1 may play an important role in the maintenance of metabolic homeostasis. Areas covered in this review: The functional effects of MKP-1 in MAPK regulation with emphasis on its role in physiological and pathophysiological signaling functions that have been elucidated through the use of mouse genetics. What the reader will gain: The reader will learn that MAPK inactivation through the effects of MKP-1 is essential for the maintenance of metabolic homeostasis. We will convey the idea that MKP-1 acts as a critical signaling node in MAPK-mediated regulation of cell signaling and metabolism. Take home message: Pharmacological inactivation of MKP-1 may be of therapeutic value in the treatment of obesity and possibly other metabolic disorders.