Calmodulin-dependent glycogen synthase kinase from rabbit skeletal muscle and calmodulin-dependent protein kinase-II from rat brain were found to have remarkably similar substrate specificities. Both protein kinases phosphorylated synapsin-I, glycogen synthase, smooth muscle myosin light chains, histone H1 and acetyl-CoA carboxylase at the same relative rates. Site-2 of glycogen synthase was preferentially phosphorylated by both enzymes, followed by a slower phosphorylation of site-1b. Each protein kinase catalysed a 2-fold activation of tryptophan 5-monooxygenase. Calmodulin-dependent protein kinase-II and glycogen synthase kinase exhibited similar immunological cross-reactivity in the presence of Ca2+ and calmodulin, using monoclonal antibody raised against the rat brain enzyme. In the absence of Ca2+ and calmodulin, cross-reactivity of glycogen synthase kinase was decreased, whereas that of calmodulin-dependent protein kinase-II was not. The two enzymes appear to represent different isoenzymes of a multifunctional calmodulin-dependent protein kinase that may mediate many of the actions of Ca2+ in mammalian tissues. The results demonstrate that calmodulin-dependent protein kinase-II is identical to calmodulin-dependent synapsin-I kinase-II, previously shown to be very similar to calmodulin-dependent glycogen synthase kinase [(1983) FEBS Lett. 163, 329-334].
- Glycogen synthesis
- Protein phosphorylation