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 an 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, γ and δ, which may or may not be coexpressed in the same tissue type. 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 10C40-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.