Demonstration of a Ca2+/calmodulin dependent protein kinase cascade in the hog heart.

Members of the Ca2+/calmodulin dependent protein kinase (CaMK) family and a CaMK cascade have been identified and well characterized in the brain, but little is known about their equivalents in the heart. Thus only CaMKII and its function have been reported so far. Therefore, we purified and characterized CaMKI and CaMK kinase (CaMKK) as an associated activator from the hog heart for the first time. The heart CaMKI was revealed to be the alpha isoform of brain CaMKI with a molecular weight of 41 kDa to phosphorylate cardiac phospholamban peptide, and to exhibit autophosphorylation requiring CaMKK. Heart CaMKK was found as a 67 kDa band and proved to be a different kinase from that in brain. These data indicate the existence of a heart specific CaMK cascade, consisting of CaMKI and CaMKK, along with CaMKII, which should be taken into account in any consideration of Ca2+ signal transduction.