The Ca2+/calmodulin-dependent protein kinases (CaM kinases) comprise a structurally related subfamily of serine/threonine kinases which include CaMKI, CaMKII and CaMKIV. CaMKII is a ubiquitously expressed serine/ threonine protein kinase that is activated by Ca2+ and calmodulin (CaM) and has been implicated in regulation of the cell cycle and transcription. There are four CaMKII isozymes, designated α, β,γandδ, which may or may not be coexpressed in the same tissue types. CaMKIV is stimulated by Ca2+ and CaM but also requires phosphorylation by a CaMK for full activation. Stimulation of the T cell receptor CD3 signaling complex with an anti-CD3 monoclonal antibody leads to a 10-40 fold increase in CaMKIV activity. An additional kinase, CaMKK, functions to activate CaMKI through the specific phosphorylation of the regulatory threonine residue at position 177.
