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 a, ∫, (C) and ?, which may or may not be co-expressed in the same tissue type. CaMKIV is stimulated by Ca2+ and CaM but phosphorylation by a CaMK is also required 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.