Calcium/calmodulin-dependent kinase IV in immune and inflammatory responses: novel routes for an ancient traveller

Ca(2+) is a pivotal second messenger controlling the activation of lymphocytes. Crucial events in the social life of immunocytes are regulated by the calcium/calmodulin complex (Ca(2+)/CaM), which controls the activation status of many enzymes, including the Ca(2+)/CaM-dependent Ser-Thr kinases (CaMK) I, II and IV. Although CaMKI and CaMKII are expressed ubiquitously, CaMKIV is found predominately in cells of the nervous and immune systems. To be active, CaMKIV requires binding of Ca(2+)/CaM and phosphorylation by CaMKK alpha or beta. The requirement of two CaM kinases in the same signalling pathway led to the concept of a CaM kinase cascade. In this review, we focus on the roles of CaMKK and CaMKIV cascades in immune and inflammatory responses.