High resolution

Module 4: Figure activation of CaMKs

Ca2+ activation of Ca2+/calmodulin-dependent protein kinases I and IV (CaMKI/CaMKIV).

Ca2+/CaM (calmodulin)-dependent protein kinase I (CaMKI) and IV (CaMKIV) are described together because they share a similar activation mechanism. The action of Ca2+ begins with it binding to CaM to form the Ca2+/CaM complex, which then has two separate actions. Firstly, it binds to the Ca2+/CaM-binding site of CaMK kinase (CaMKK), resulting in a conformational change that leads to the activation of the catalytic domain. In its second action, Ca2+/CaM binds to CaMKI or CaMKIV, causing a similar conformational change that then enables the activated CaMKK to phosphorylate a threonine residue on the activation loops of CaMKI (Thr-177) or CaMKIV (Thr-196), which are then able to phosphorylate their substrates.