Ca2+-calmodulin and protein kinase Cs:: a hypothetical synthesis of their conflicting convergences on shared substrate domains

Evidence is accumulating that suggests that Ca2+-calmodulin (Ca2+-CaM) and the protein kinase Cs (PKCs) obstruct each other's actions because of the embedding of PKC phosphorylation sites in CaM or Ca2+-CaM-binding domains of a growing number of crucial substrates in neurons land other cells). These substrates include the CaM storage proteins (neurogranin, neuromodulin), the membrane-associated MARCKS (myristoylated alanine rich C-kinase substrate) protein, the NMDA receptor RI subunit and the autoinhibitory domain of the plasma membrane Ca2+ pump. In this review, the emerging data are woven into a hypothetical picture of the conflicting, timing-dependent convergence of two major signalers on neuronal functions.