Opposing forces in asthma: regulation of signaling pathways by kinases and phosphatases

Abstract

Allergic asthma is a chronic inflammatory disease that involves a sustained T-helper-2 (Th2) type immune response and the recruitment of inflammatory cells such as lymphocytes, mast cells, and eosinophils to the lung. The complex cellular interactions involved in this disease are dependent on cellular responses generated following the integration of environmental signals through the cell signaling pathways. Therefore, the elucidation of the biochemical cascades involved in cellular responses contributing to asthma development has been of great interest in this field. Much attention has been given to the activities of kinases, enzymes that catalyze the addition of a phosphate group to a protein, thus allowing them to modify the function of the target enzyme. This resulted in the identification of key kinases and various cellular processes involved in disease development. New investigations have also begun to unravel the importance of phosphatases, which catalyze the removal of a phosphate group from their target protein. Together, these studies reveal a signaling picture in allergic asthma that is far more complex than originally thought. Herein, we review critical mechanisms of asthma development and discuss how kinases and phosphatases are likely to regulate the development of disease through their effect on these various mechanisms.