Table 1.

Summary of the features of multifunctional CaMKs^a

	CaMKI	CaMKII	CaMKIV
Structure	Monomeric (∼40 kDa)	Oligomeric (∼550 kDa) (subunit=50–60 kDa)	Monomeric (∼60 kDa)
Distribution
Tissue	Ubiquitous	Ubiquitous, abundant in brain	Limited (abundant in brain and thymus)
Subcellular	Cytosol	PSD and cytosol	Nucleus
Substrates	Synapsin I, CFTR, CREB, Numb, Numbl and others	Tyrosine hydroxylase, tryptophan hydroxylase, synapsin I, GluR1, glycogen synthase, MAP2, phospholamban and others	Synapsin I, MAP2, myelin basic protein, Rap-1b, CREB, SRF, MEF2, ATF1/2 and others
Physiological roles	Transcription, cell-cycle regulation	Carbohydrate metabolism, neurotransmitter synthesis/release, transcription, cytoskeletal organization, LTP, neuronal memory, cardiac functions and others	Transcription, spermatogenesis, LTP, neuronal memory, mitochondrial biogenesis, osteogenesis and others
Diseases in which the kinase may be involved	Cancer	Learning disorder, Angelman's syndrome, Parkinson's disease, Alzheimer's disease, delayed neuronal death, cardiac hypertrophy, arrhythmia, cardiomyocyte apoptosis, diabetes, cancer	Learning disorder, delayed neuronal death, cardiac hypertrophy, osteoporosis
Inhibitors	KN-62, CaMKI (294–321), KN-93	CaMKII (281–309), CaMKII (273–302), KN-62, KN-93, AIP, AC3-I, CaMKIIN, CN21, PEP-19	KN-62, KN-93
Activation mechanism	Activated upon phosphorylation by CaMKK on Thr-177 located in activation loop	Activated upon autophosphorylation on Thr-286 located in autoinhibitory domain	Activated upon phosphorylation by CaMKK on Thr-196 located in activation loop
Dephosphorylating protein phosphatase	PP2A, CaMKP, CaMKP-N	PP1, PP2A, PP2C, CaMKP, CaMKP-N	PP1, PP2A, PP2B, PP2C, CaMKP, CaMKP-N

Abbreviations: AIP, autocamtide-2-related inhibitory peptide; ATF, activating transcription factor; CaMK, Ca²⁺/calmodulin-dependent protein kinase; CaMKK, CaMK kinase; CaMKP, CaMK phosphatase; CFTR, cystic fibrosis transmembrane conductance regulator; CREB, cAMP response element-binding protein; LTP, long-term potentiation; MAP2, microtubule associated protein 2; MEF2, myocyte enhancer factor 2; PP, protein phosphatase; PSD, postsynaptic density; SRF, serum response factor.

^aAdapted from Ishida et al. (2003).