Regulation of multifunctional Ca2+/calmodulin-dependent protein kinases byCa2+/calmodulin-dependent protein kinase phosphatase

We have recently reported a novel protein phosphatase which dephosphorylate s and thereby deactivates Ca2+/calmodulin-dependent protein kinase II (CaMK II) activated through autophosphorylation (Ishida, A., Kameshita, I., and F ujisawa, H. (1998) J. Biol. Chem. 273, 1904-1910), In the present study, we show that this protein phosphatase also catalyzed dephosphorylation of Ca2 +/calmodulin-dependent protein kinases I (CaMKI) and IV (CaMKIV) which had been phosphorylated and activated by Ca2+/calmodulin-dependent protein kina se kinase alpha, resulting in reversible deactivation of the enzymes. The f airly high degree of the substrate specificity of this protein phosphatase suggests that the physiological significance of the phosphatase may be the regulation of the three multifunctional Ca2+/calmodulin-dependent protein k inases, CaMKI, CaMKII, and CaMKIV, which are the key enzymes in a Ca2+-sign aling system in the cell. (C) 1998 Academic Press.