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Gene Review

Camk2a  -  calcium/calmodulin-dependent protein...

Mus musculus

Synonyms: CaM kinase II subunit alpha, CaMK-II subunit alpha, CaMKII, Calcium/calmodulin-dependent protein kinase type II subunit alpha, R74975, ...
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Disease relevance of Camk2a


Psychiatry related information on Camk2a


High impact information on Camk2a


Chemical compound and disease context of Camk2a

  • In addition, presynaptic injection of the membrane-impermeable CaMKII inhibitor peptide 281-309 blocked synaptic plasticity induced by tetanus, glutamate, or NO/cGMP pathway activation as expressed by long-lasting increases in EPSC amplitude and functional presynaptic boutons [10].
  • The NMDA-induced CaMKII activation in the hippocampal slices of wild-type mice was significantly inhibited by exogenous nociceptin via a pertussis toxin-sensitive pathway [11].
  • In conclusion, our results suggest that CaMKII, activated through NMDA receptors and L-VGCCs, mediated the serine phosphorylation of GluR6 during brain ischemia and early reperfusion period [12].
  • Pre-incubation with the phospholipase C (PLC) inhibitor U73122 (10 microM), L-type Ca(2+)-channel blockers nifedipine (1 microM) and nimodipine (1 microM), the calmodulin kinase II (CaMKII) inhibitor KN-62 (10 microM) or pertussis toxin (100 ng/ml) inhibited this potentiation [13].

Biological context of Camk2a


Anatomical context of Camk2a

  • The purpose of this study was to examine the expression of CaMKII in osteoblast-like cells (MC4) and to elucidate its role in osteoblast differentiation [16].
  • In combination, these data support a model in which [P-T286]CaMKIIalpha can simultaneously interact with multiple dendritic spine proteins, possibly stabilizing the synaptic localization of CaMKII and/or nucleating a multiprotein synaptic signaling complex [17].
  • CaM and CaMKII antagonists, using the newborn mouse calvaria in vivo model, cause a 50% decrease in osteoblast number (N.Ob-BS) and a 32% decrease in mineralization (BV/TV) [16].
  • No significant alterations in CaMKII or CaN immunolabelling were observed in the hippocampus of kainic acid-treated mice [18].
  • We hypothesized that chronic CaMKII inhibition significantly affects CICR in ventricular myocytes [19].

Associations of Camk2a with chemical compounds

  • NR2B inhibits both the Ca(2+)/calmodulin-dependent and autonomous activities of CaMKII by a mechanism that is competitive with autocamtide-2 substrate, non-competitive with syntide-2 substrate, and uncompetitive with respect to ATP [20].
  • Our results suggest that the expression of CaMKII and CaN mRNAs is down-regulated in neuronal cells in response to the hyperexcitability induced by kainic acid [18].
  • PLN ablation eliminated I(Ca) facilitation even in the absence of CaMKII inhibition and the effects of CaMKII inhibition to reduce SR Ca(2+) content and slow SR Ca(2+) uptake were lost in the absence of PLN [19].
  • KN-93, a Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) inhibitor, concentration-dependently and reversibly inhibited inositol 1,4,5-trisphosphate receptor (IP(3)R)-mediated [Ca(2+)](i) signaling in mouse eggs and permeabilized A7r5 smooth muscle cells, two cell types predominantly expressing type-1 IP(3)R (IP(3)R-1) [21].
  • Finally we show that disrupting either NMDA or calcium/calmodulin-dependent kinase II (CaMKII) function impairs consolidation of context memories [22].

Physical interactions of Camk2a

  • Nonphosphorylated and Thr(286)-autophosphorylated CaMKII bind to alpha-actinin with similar efficacy, but autophosphorylation at Thr(305/306) or Ca(2+)/calmodulin binding significantly reduce this binding [20].
  • In addition, the CaMKII binding domain of densin-180 has little effect on CaMKII activity [20].
  • Following basal autophosphorylation, the calmodulin-binding ability of CaMKII was also reduced, presumably accounting for the observed inactivation [23].
  • We have previously shown that autophosphorylation of CaMKII induces high-affinity binding to the NR2B subunit of the NMDA receptor (Strack, S., and Colbran, R. J. (1998) J. Biol. Chem. 273, 20689-20692) [24].

Enzymatic interactions of Camk2a

  • Purified rat forebrain CaMKII was also able to phosphorylate gp130 fusion protein at Ser782 in vitro [25].
  • Two-dimensional phosphopeptide mapping demonstrated that the site phosphorylated in vitro by CaMKII was also phosphorylated in intact astrocytes in response to endothelin [26].
  • Furthermore, activated CaMKII directly phosphorylated the recombinant COOH-terminal region of FAK at a residue equivalent to Ser-843 [27].

Regulatory relationships of Camk2a


Other interactions of Camk2a

  • Overall, our results indicated that radixin via its C-terminal domain mediates SRE-dependent gene transcription through activation of Rac1 and CaMKII [15].
  • Radixin stimulates Rac1 and Ca2+/calmodulin-dependent kinase, CaMKII: cross-talk with Galpha13 signaling [15].
  • Taken together, in OBX mice NMDA receptor hypofunction, possibly through decreased PKCalpha activity, underlies decreased CaMKII activity in the post-synaptic regions, thereby impairing LTP induction in the hippocampal CA1 region [5].
  • Moreover, PLB phosphorylation by CaMKII plays an important role in limiting the decline in Ca transients (and contraction) during acidosis [4].
  • In 12-month-old GC-A-/- hearts only, dispersion of APD and expression levels of CaMKII were increased [3].

Analytical, diagnostic and therapeutic context of Camk2a

  • Ca(2+)/Camodulin-dependent protein kinase II (CaMKII) is a multifunctional enzyme that is postulated to be the downstream transducer of the Ca(2+) signal in many cell types [31].
  • Cardiac expression of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) was analyzed by western blotting [3].
  • These results suggest that additive activation by ERK and CaMKII, most likely as a result of photic stimulation in the suprachiasmatic nucleus, plays a critical role in activating the mPer1 gene promoter [32].
  • We also show by electron microscopy that in its fully assembled form the CaMKII holoenzyme is a dodecamer but without the kinase domains, either from expression of the isolated association domain in bacteria or following their removal by proteolysis, the association domains form a tetradecamer [33].
  • The activity and expression of protein phosphatase 2A were both found to be increased in CaMKII TG mice, and immunoprecipitation studies indicated that protein phosphatase 2A directly associates with CaMKII [34].


  1. Calmodulin kinase II inhibition protects against structural heart disease. Zhang, R., Khoo, M.S., Wu, Y., Yang, Y., Grueter, C.E., Ni, G., Price, E.E., Thiel, W., Guatimosim, S., Song, L.S., Madu, E.C., Shah, A.N., Vishnivetskaya, T.A., Atkinson, J.B., Gurevich, V.V., Salama, G., Lederer, W.J., Colbran, R.J., Anderson, M.E. Nat. Med. (2005) [Pubmed]
  2. Pressure overload selectively up-regulates Ca2+/calmodulin-dependent protein kinase II in vivo. Colomer, J.M., Mao, L., Rockman, H.A., Means, A.R. Mol. Endocrinol. (2003) [Pubmed]
  3. Ventricular arrhythmias, increased cardiac calmodulin kinase II expression, and altered repolarization kinetics in ANP receptor deficient mice. Kirchhof, P., Fabritz, L., Kilić, A., Begrow, F., Breithardt, G., Kuhn, M. J. Mol. Cell. Cardiol. (2004) [Pubmed]
  4. Phospholamban is required for CaMKII-dependent recovery of Ca transients and SR Ca reuptake during acidosis in cardiac myocytes. DeSantiago, J., Maier, L.S., Bers, D.M. J. Mol. Cell. Cardiol. (2004) [Pubmed]
  5. Decreased calcium/calmodulin-dependent protein kinase II and protein kinase C activities mediate impairment of hippocampal long-term potentiation in the olfactory bulbectomized mice. Moriguchi, S., Han, F., Nakagawasai, O., Tadano, T., Fukunaga, K. J. Neurochem. (2006) [Pubmed]
  6. Changes in phosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in processing of short-term and long-term memories after passive avoidance learning. Zhao, W., Lawen, A., Ng, K.T. J. Neurosci. Res. (1999) [Pubmed]
  7. Metabolic regulation of oocyte cell death through the CaMKII-mediated phosphorylation of caspase-2. Nutt, L.K., Margolis, S.S., Jensen, M., Herman, C.E., Dunphy, W.G., Rathmell, J.C., Kornbluth, S. Cell (2005) [Pubmed]
  8. Common molecular pathways mediate long-term potentiation of synaptic excitation and slow synaptic inhibition. Huang, C.S., Shi, S.H., Ule, J., Ruggiu, M., Barker, L.A., Darnell, R.B., Jan, Y.N., Jan, L.Y. Cell (2005) [Pubmed]
  9. A role for CaMKII in T cell memory. Bui, J.D., Calbo, S., Hayden-Martinez, K., Kane, L.P., Gardner, P., Hedrick, S.M. Cell (2000) [Pubmed]
  10. Presynaptic CaMKII is necessary for synaptic plasticity in cultured hippocampal neurons. Ninan, I., Arancio, O. Neuron (2004) [Pubmed]
  11. Neuronal mechanism of nociceptin-induced modulation of learning and memory: involvement of N-methyl-D-aspartate receptors. Mamiya, T., Yamada, K., Miyamoto, Y., König, N., Watanabe, Y., Noda, Y., Nabeshima, T. Mol. Psychiatry (2003) [Pubmed]
  12. Calcium/calmodulin-dependent protein kinase II (CaMKII), through NMDA receptors and L-Voltage-gated channels, modulates the serine phosphorylation of GluR6 during cerebral ischemia and early reperfusion period in rat hippocampus. Hao, Z.B., Pei, D.S., Guan, Q.H., Zhang, G.Y. Brain Res. Mol. Brain Res. (2005) [Pubmed]
  13. Astrocyte mGlu(2/3)-mediated cAMP potentiation is calcium sensitive: studies in murine neuronal and astrocyte cultures. Moldrich, R.X., Apricó, K., Diwakarla, S., O'Shea, R.D., Beart, P.M. Neuropharmacology (2002) [Pubmed]
  14. Autophosphorylation at Thr286 of the alpha calcium-calmodulin kinase II in LTP and learning. Giese, K.P., Fedorov, N.B., Filipkowski, R.K., Silva, A.J. Science (1998) [Pubmed]
  15. Radixin stimulates Rac1 and Ca2+/calmodulin-dependent kinase, CaMKII: cross-talk with Galpha13 signaling. Liu, G., Voyno-Yasenetskaya, T.A. J. Biol. Chem. (2005) [Pubmed]
  16. Calmodulin and calmodulin-dependent kinase IIalpha regulate osteoblast differentiation by controlling c-fos expression. Zayzafoon, M., Fulzele, K., McDonald, J.M. J. Biol. Chem. (2005) [Pubmed]
  17. Multivalent interactions of calcium/calmodulin-dependent protein kinase II with the postsynaptic density proteins NR2B, densin-180, and alpha-actinin-2. Robison, A.J., Bass, M.A., Jiao, Y., MacMillan, L.B., Carmody, L.C., Bartlett, R.K., Colbran, R.J. J. Biol. Chem. (2005) [Pubmed]
  18. Decreased expression of calmodulin kinase II and calcineurin messenger RNAs in the mouse hippocampus after kainic acid-induced seizures. Solà, C., Tusell, J.M., Serratosa, J. J. Neurochem. (1998) [Pubmed]
  19. Suppression of dynamic Ca(2+) transient responses to pacing in ventricular myocytes from mice with genetic calmodulin kinase II inhibition. Wu, Y., Shintani, A., Grueter, C., Zhang, R., Hou, Y., Yang, J., Kranias, E.G., Colbran, R.J., Anderson, M.E. J. Mol. Cell. Cardiol. (2006) [Pubmed]
  20. Differential modulation of Ca2+/calmodulin-dependent protein kinase II activity by regulated interactions with N-methyl-D-aspartate receptor NR2B subunits and alpha-actinin. Robison, A.J., Bartlett, R.K., Bass, M.A., Colbran, R.J. J. Biol. Chem. (2005) [Pubmed]
  21. Inhibition of the inositol trisphosphate receptor of mouse eggs and A7r5 cells by KN-93 via a mechanism unrelated to Ca2+/calmodulin-dependent protein kinase II antagonism. Smyth, J.T., Abbott, A.L., Lee, B., Sienaert, I., Kasri, N.N., De Smedt, H., Ducibella, T., Missiaen, L., Parys, J.B., Fissore, R.A. J. Biol. Chem. (2002) [Pubmed]
  22. Consolidation of CS and US representations in associative fear conditioning. Frankland, P.W., Josselyn, S.A., Anagnostaras, S.G., Kogan, J.H., Takahashi, E., Silva, A.J. Hippocampus. (2004) [Pubmed]
  23. Inactivation of Ca2+/calmodulin-dependent protein kinase II by basal autophosphorylation. Colbran, R.J. J. Biol. Chem. (1993) [Pubmed]
  24. Mechanism and regulation of calcium/calmodulin-dependent protein kinase II targeting to the NR2B subunit of the N-methyl-D-aspartate receptor. Strack, S., McNeill, R.B., Colbran, R.J. J. Biol. Chem. (2000) [Pubmed]
  25. Calmodulin-dependent protein kinases phosphorylate gp130 at the serine-based dileucine internalization motif. Gibson, R.M., Laszlo, G.S., Nathanson, N.M. Biochim. Biophys. Acta (2005) [Pubmed]
  26. Endothelin induces a calcium-dependent phosphorylation of PEA-15 in intact astrocytes: identification of Ser104 and Ser116 phosphorylated, respectively, by protein kinase C and calcium/calmodulin kinase II in vitro. Kubes, M., Cordier, J., Glowinski, J., Girault, J.A., Chneiweiss, H. J. Neurochem. (1998) [Pubmed]
  27. G protein-coupled receptor activation rapidly stimulates focal adhesion kinase phosphorylation at Ser-843. Mediation by Ca2+, calmodulin, and Ca2+/calmodulin-dependent kinase II. Fan, R.S., Jácamo, R.O., Jiang, X., Sinnett-Smith, J., Rozengurt, E. J. Biol. Chem. (2005) [Pubmed]
  28. CaM kinase II and phospholamban contribute to caffeine-induced relaxation of murine gastric fundus smooth muscle. Kim, M., Cho, S.Y., Han, I.S., Koh, S.D., Perrino, B.A. Am. J. Physiol., Cell Physiol. (2005) [Pubmed]
  29. Activation of the rat dopamine D2 receptor promoter by mitogen-activated protein kinase and Ca2+/calmodulin-dependent protein kinase II pathways. Takeuchi, Y., Miyamoto, E., Fukunaga, K. J. Neurochem. (2002) [Pubmed]
  30. Photoreceptor regulated expression of Ca(2+)/calmodulin-dependent protein kinase II in the mouse retina. Liu, L.O., Li, G., McCall, M.A., Cooper, N.G. Brain Res. Mol. Brain Res. (2000) [Pubmed]
  31. Calmodulin-dependent protein kinase II triggers mouse egg activation and embryo development in the absence of Ca2+ oscillations. Knott, J.G., Gardner, A.J., Madgwick, S., Jones, K.T., Williams, C.J., Schultz, R.M. Dev. Biol. (2006) [Pubmed]
  32. MAP kinase additively activates the mouse Per1 gene promoter with CaM kinase II. Nomura, K., Takeuchi, Y., Fukunaga, K. Brain Res. (2006) [Pubmed]
  33. Oligomerization states of the association domain and the holoenyzme of Ca2+/CaM kinase II. Rosenberg, O.S., Deindl, S., Comolli, L.R., Hoelz, A., Downing, K.H., Nairn, A.C., Kuriyan, J. FEBS J. (2006) [Pubmed]
  34. The cardiac-specific nuclear delta(B) isoform of Ca2+/calmodulin-dependent protein kinase II induces hypertrophy and dilated cardiomyopathy associated with increased protein phosphatase 2A activity. Zhang, T., Johnson, E.N., Gu, Y., Morissette, M.R., Sah, V.P., Gigena, M.S., Belke, D.D., Dillmann, W.H., Rogers, T.B., Schulman, H., Ross, J., Brown, J.H. J. Biol. Chem. (2002) [Pubmed]
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