Antigen: rat recombinant CaMKII · Clone designation: clone 6G9 · Host: mouse · Isotype: IgG₁ · Application(s): IF, IP, WB, IHC, and ELISA · CaMKII is an important member of the calcium/calmodulin-activated protein kinase family, functioning in neural synaptic stimulation and T-cell receptor signaling.^1,2 CaMKII is expressed in many different tissues but is specifically found in neurons of the forebrain and its mRNA is found within the dendrites and the soma of the neuron. The CaMKII that is found in the neurons consist of two subunits of 52 (termed α genes) and 60 kDa (β genes). CaMKII has catalytic and regulatory domains, as well as an ATP-binding domain, and a consensus phosphorylation site.^3,4,5,6,7 The binding of Ca2+/calmodulin to its regulatory domain releases its auto inhibitory effect and activates the kinase.⁸ This kinase activation results in autophosphorylation at threonine 286 (Thr²⁸⁶).⁸ The threonine phosphorylation state of CaMKII can be regulated through protein phosphatase 1 (PP1)/protein kinase A (PKA). Whereas PP1 dephosphorylates phospho-CaMKII at Thr²⁸⁶, PKA prevents this dephosphorylation.⁹ Autophosphorylation also enables CaMKII to attain an enhanced affinity for NMDA receptors in postsynaptic densities.^10,11,12

1 Hughes, K., Edin, S., Antonsson Å, et al. Calmodulin-dependent kinase II mediates T cell receptor/CD3- and phorbol ester-induced activation of IkB kinase. J Biol Chem 276(38) 36008-36013 (2001).

2 Barria, A., Muller, D., Derkach, V., et al. Regulatory phosphorylation of AMPA-type glutamate receptors by CaM-KII during long-term potentiation. Science 276 2042-2045 (1997).

3 Bennett, M.K., and Kennedy, M.B. Deduced primary structure of the b subunit of brain type II Ca2+/calmodulin-dependent protein kinase determined by molecular cloning. Proc Natl Acad Sci USA 84 1794-1798 (1987).

4 Brocke, L., Srinivassan, M., and Schulman, H. Development and regional expression of multifunctional Ca2+/calmodulin-dependent protein kinase isoforms in rat brain. J Neurosci 15(10) 6797-6808 (1995).

5 Nghiem, P., Saati, S.M., Martens, C.L., et al. Cloning and analysis of two new isoforms of multifunctional Ca2+/calmodulin-dependent protein kinase. Expression in multiple human tissues. J Biol Chem 268(8) 5471-5479 (1983).

6 Edman, C.F., and Schulman, H. Identification and characterization of delta B-CaM kinase and delta C-Cam kinase from rat heart, two new multifunctional Ca2+/calmodulin-dependent protein kinase isoforms. Biochim Biophys Acta 1221(1) 89-101 (1994).

7 Tombes, R.M., and Krystal, G.W. Identification of novel human tumor cell-specific CaMK-II variants. Biochim Biophys Acta 1355(3) 281-292 (1997).

8 Means, A.R. Regulatory cascades involving calmodulin-dependent protein kinases. Mol Endocrinol 14(1) 4-13 (2000).

9 Makhinson, M., Chotiner, J.K., Watson, J.B., et al. Adenylyl cyclase activation modulates activity-dependent changes in synaptic strength and Ca2+/calmodulin-dependent kinase II autophosphorylation. J Neurochem 19(7) 2500-2510 (1999).

10 Strack, S., and Colbran, R.J. Autophosphorylation-dependent targeting of calcium/calmodulin-dependent protein kinase II by the NR2B subunit of the N-methyl-D-aspartate receptor. J Biol Chem 273(33) 20689-20692 (1998).

11 Leonard, A.S., Lim, I.A., Hemsworth, D.E., et al. Calcium/calmodulin-dependent protein kinase II is associated with the N-methyl-D-aspartate receptor. Proc Natl Acad Sci USA 96 3239-3244 (1999).

12 Shen, K., and Meyer, T. Dynamic control of CaMKII translocation and localization in hippocampal neurons by NMDA receptor stimulation. Science 284 162-167 (1999).

Strack, S., and Colbran, R.J. Autophosphorylation-dependent targeting of calcium/calmodulin-dependent protein kinase II by the NR2B subunit of the N-methyl-D-aspartate receptor. J Biol Chem 273(33) 20689-20692 (1998).

Makhinson, M., Chotiner, J.K., Watson, J.B., et al. Adenylyl cyclase activation modulates activity-dependent changes in synaptic strength and Ca2+/calmodulin-dependent kinase II autophosphorylation. J Neurochem 19(7) 2500-2510 (1999).

Tombes, R.M., and Krystal, G.W. Identification of novel human tumor cell-specific CaMK-II variants. Biochim Biophys Acta 1355(3) 281-292 (1997).

Barria, A., Muller, D., Derkach, V., et al. Regulatory phosphorylation of AMPA-type glutamate receptors by CaM-KII during long-term potentiation. Science 276 2042-2045 (1997).

Brocke, L., Srinivassan, M., and Schulman, H. Development and regional expression of multifunctional Ca2+/calmodulin-dependent protein kinase isoforms in rat brain. J Neurosci 15(10) 6797-6808 (1995).

Nghiem, P., Saati, S.M., Martens, C.L., et al. Cloning and analysis of two new isoforms of multifunctional Ca2+/calmodulin-dependent protein kinase. Expression in multiple human tissues. J Biol Chem 268(8) 5471-5479 (1983).

Edman, C.F., and Schulman, H. Identification and characterization of delta B-CaM kinase and delta C-Cam kinase from rat heart, two new multifunctional Ca2+/calmodulin-dependent protein kinase isoforms. Biochim Biophys Acta 1221(1) 89-101 (1994).

Bennett, M.K., and Kennedy, M.B. Deduced primary structure of the b subunit of brain type II Ca2+/calmodulin-dependent protein kinase determined by molecular cloning. Proc Natl Acad Sci USA 84 1794-1798 (1987).

Hughes, K., Edin, S., Antonsson Å, et al. Calmodulin-dependent kinase II mediates T cell receptor/CD3- and phorbol ester-induced activation of IkB kinase. J Biol Chem 276(38) 36008-36013 (2001).

Means, A.R. Regulatory cascades involving calmodulin-dependent protein kinases. Mol Endocrinol 14(1) 4-13 (2000).

Shen, K., and Meyer, T. Dynamic control of CaMKII translocation and localization in hippocampal neurons by NMDA receptor stimulation. Science 284 162-167 (1999).

Leonard, A.S., Lim, I.A., Hemsworth, D.E., et al. Calcium/calmodulin-dependent protein kinase II is associated with the N-methyl-D-aspartate receptor. Proc Natl Acad Sci USA 96 3239-3244 (1999).

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