Sequences of autophosphorylation sites in neuronal type II CaM kinase that control Ca2(+)-independent activity.
After initial activation by Ca2+, the catalytic activity of type II Ca2+/calmodulin-dependent protein kinase rapidly becomes partially independent of Ca2+. The transition is caused by autophosphorylation of a few subunits in the dodecameric holoenzyme, which is composed of varying proportions of two homologous types of subunits, alpha (50 kd) and beta (58-60 kd). We have identified one site in the alpha subunit (Thr286) and two in the beta subunit (Thr287 and Thr382) that are rapidly autophosphorylated. We show that phosphorylation of alpha-Thr286 and beta-Thr287, which are located immediately adjacent to the calmodulin binding domain, controls Ca2(+)-independent activity. In contrast, phosphorylation of beta-Thr382 is not required to maintain Ca2+ independence. It is absent in the alpha subunit and is selectively removed from the minor beta' subunit, apparently by alternative splicing. Regulation of the presence of beta-Thr382 in the holoenzyme by both differential gene expression and alternative splicing suggests that it may have an important but highly specialized function.
Miller
S G
SG
Division of Biology, California Institute of Technology, Pasadena 91125.
Patton
B L
BL
Kennedy
M B
MB
D000818:Animals; D001921:Brain / Q000201:enzymology*; D001923:Brain Chemistry; D002118:Calcium / Q000502:physiology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002417:Cattle; D066298:In Vitro Techniques; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*
D011494:Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium