Cross-kingdom regulation of calcium- and/or calmodulin-dependent protein kinases by phospho-switches that relieve autoinhibition

Mechanisms to sense and respond to calcium have evolved in all organisms. Calmodulin is a universal calcium sensor across eukaryotes that directly binds calcium and associates with many downstream signal transducers including protein kinases. All eukaryotes encode calcium-dependent and/or calmodulin-dependent kinases, however there are distinct protein families across kingdoms. Here, we compare the activation mechanisms of calmodulin-dependent protein kinases (CaMKs), calcium- and calmodulin-dependent protein kinases (CCaMKs) and calcium-dependent protein kinases (CDPKs), noting striking similarities regarding phosphorylation in a regulatory segment known as the autoinhibitory junction. We thus propose that conserved regulation by phosphorylation underlies the activation of calcium-responsive proteins from different kingdoms.