CA2+ CALMODULIN-DEPENDENT PROTEIN-KINASE KINASE CASCADE/

Recently we obtained evidence for the existence of Ca2+/calmodulin-dep endent protein kinase kinase(CaMKK), which was partially purified in t he process of the purification step of Ca2+/calmodulin-dependent prote in kinase V (CaM kinase V). This enzyme promoted phosphorylation of th e autophosphorylation site on CaM kinase V and activated the activity( Mochizuki, H. et al. (1993) Biochem. Biophys. Res. Commun. 197, 1595-1 600). Present study revealed that CaMKK also phosphorylated CaM kinase IV associated with the activation of its activity. Phosphorylation of CaM kinase IV by CaMKK occurred on multiple sites. Furthermore, CaM k inase IV and CaM kinase V phosphorylated each other which resulted in their activation. The phosphorylation site of CaM kinase V by CaM kina se IV was the same as the autophosphorylation site. Our study suggests the existence of a heretofore CaM kinases cascade consisting of a seq uential activation of each CaM kinase. [Graphics] (C) 1994 Academic Pr ess, Inc.