Activation of Ca(2+)-calmodulin-dependent protein kinase Ia is due to direct phosphorylation by its activator.
Ca(2+)-Calmodulin-dependent protein kinase Ia (CaM kinase Ia) is phosphorylated, and its activity enhanced up to 50-fold, in the presence of a protein purified from pig brain termed CaM kinase Ia activator [Lee, J.C. and Edelman, A.M. (1994) J. Biol. Chem. 269, 2158-2164]. We report here that phosphorylation of CaM kinase Ia in the presence of the activator occurs primarily on threonine (87%) and slightly on serine (13%) residues. Treatment of CaM kinase Ia with the irreversible ATP affinity analogue, 5'-p-fluorosulfonylbenzoyl adenosine (FSBA), reduces its activity by 86% but has no effect on its ability to be phosphorylated, whereas FSBA-treatment of the activator reduces its ability to activate and phosphorylate CaM kinase Ia by 92 and 93%, respectively. Thus, CaM kinase Ia activator is a protein Thr/Ser kinase which activates by phosphorylating CaM kinase Ia rather than by enhancing the latter's autophosphorylation.
Lee
J C
JC
Department of Pharmacology and Toxicology, State University of New York at Buffalo, New York 14214, USA.
Edelman
A M
AM
D000241:Adenosine / Q000031:analogs & derivatives; D000345:Affinity Labels; D000595:Amino Acid Sequence; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D013552:Swine
D000345:Affinity Labels; C010959:5'-(4-fluorosulfonylbenzoyl)adenosine; D011494:Protein Kinases; C106686:(CaM)-dependent protein kinase Ia kinase; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D000241:Adenosine