Gene Symbol: Camk2a
Description: calcium/calmodulin-dependent protein kinase II alpha
Alias: PK2CDD, PKCCD, calcium/calmodulin-dependent protein kinase type II subunit alpha, Ca2+/calmodulin-dependent protein kinase II alpha, alpha CaM kinase II, caM kinase II subunit alpha, caM-kinase II alpha chain, caMK-II subunit alpha, calcium/calmodulin-dependent protein kinase (CaM kinase) II alpha, calcium/calmodulin-dependent protein kinase II alpha subunit, calcium/calmodulin-dependent protein kinase type II alpha chain
Species: rat
Products:     Camk2a

Top Publications

  1. Xu G, Huang L. Ca2+/calmodulin-dependent protein kinase II potentiates ATP responses by promoting trafficking of P2X receptors. Proc Natl Acad Sci U S A. 2004;101:11868-73 pubmed
  2. Okamoto K, Narayanan R, Lee S, Murata K, Hayashi Y. The role of CaMKII as an F-actin-bundling protein crucial for maintenance of dendritic spine structure. Proc Natl Acad Sci U S A. 2007;104:6418-23 pubmed
    ..This finding indicates that CaMKII serves as a central signaling molecule in both functional and structural changes during synaptic plasticity. ..
  3. Padmanabhan S, Lambert N, Prasad B. Activity-dependent regulation of the dopamine transporter is mediated by Ca(2+)/calmodulin-dependent protein kinase signaling. Eur J Neurosci. 2008;28:2017-27 pubmed publisher
    ..These data suggest that neuronal activity can regulate dopamine transporter function and abundance via calcium/CaM kinase II signaling. ..
  4. Rose J, Jin S, Craig A. Heterosynaptic molecular dynamics: locally induced propagating synaptic accumulation of CaM kinase II. Neuron. 2009;61:351-8 pubmed publisher
    ..L-IPS translocation of CaMKII alters biochemical signaling and is associated with an increase in AMPA receptor GluR1 at both stimulated and nonstimulated synapses and thus provides a molecular mechanism for heterosynaptic plasticity. ..
  5. Song M, Seo H, Yang M, Kim J, Kim S, Kim J, et al. Activation of Ca2+/calmodulin-dependent protein kinase II alpha in the spinal cords of rats with clip compression injury. Brain Res. 2009;1271:114-20 pubmed publisher
  6. Asrican B, Lisman J, Otmakhov N. Synaptic strength of individual spines correlates with bound Ca2+-calmodulin-dependent kinase II. J Neurosci. 2007;27:14007-11 pubmed
    ..The results are consistent with the hypothesis that bound CaMKII serves as a structural organizer of postsynaptic molecules and thereby may be involved in maintaining spine size and synaptic strength. ..
  7. Bayer K, Lebel E, McDonald G, O Leary H, Schulman H, De Koninck P. Transition from reversible to persistent binding of CaMKII to postsynaptic sites and NR2B. J Neurosci. 2006;26:1164-74 pubmed
    ..This activity-dependent incorporation of CaMKII into postsynaptic sites may play a role in maturation and plasticity of synapses. ..
  8. Vest R, O Leary H, Coultrap S, Kindy M, Bayer K. Effective post-insult neuroprotection by a novel Ca(2+)/ calmodulin-dependent protein kinase II (CaMKII) inhibitor. J Biol Chem. 2010;285:20675-82 pubmed publisher
    ..Together, these data demonstrate that inhibition of autonomous CaMKII activity provides a promising therapeutic avenue for post-insult neuro-protection after stroke...
  9. Salas M, Valverde C, Sanchez G, Said M, Rodriguez J, Portiansky E, et al. The signalling pathway of CaMKII-mediated apoptosis and necrosis in the ischemia/reperfusion injury. J Mol Cell Cardiol. 2010;48:1298-306 pubmed publisher
    ..The results reveal an apoptotic-necrotic pathway mediated by CaMKII-dependent phosphorylations at the SR, which involves the reverse NCX mode and the mitochondria as trigger and end effectors, respectively, of the cascade. ..

More Information


  1. Chen Y, Jiang Y, Yue W, Zhou Y, Lu L, Ma L. Chronic, but not acute morphine treatment, up-regulates alpha-Ca2+/calmodulin dependent protein kinase II gene expression in rat brain. Neurochem Res. 2008;33:2092-8 pubmed publisher
    ..Taken together, our data demonstrate that chronic morphine treatment region-specific up-regulates the levels of the alpha-CaMK II gene expression in hippocampus and frontal cortex. ..
  2. Lu W, Isozaki K, Roche K, Nicoll R. Synaptic targeting of AMPA receptors is regulated by a CaMKII site in the first intracellular loop of GluA1. Proc Natl Acad Sci U S A. 2010;107:22266-71 pubmed publisher
    ..Furthermore, we show that S567 is a key residue that regulates Loop1-mediated AMPAR trafficking. Thus, our study reveals a unique mechanism for targeting AMPARs to synapses to mediate synaptic transmission. ..
  3. Jones T, Lustig A, Sorkin L. Secondary hyperalgesia in the postoperative pain model is dependent on spinal calcium/calmodulin-dependent protein kinase II alpha activation. Anesth Analg. 2007;105:1650-6, table of contents pubmed
    ..Spinal sensitization underlying incision-evoked hyperalgesia involves spinal CaMKIIalpha activation and enhanced spinal alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid receptor (AMPA) function. ..
  4. Shen K, Meyer T. Dynamic control of CaMKII translocation and localization in hippocampal neurons by NMDA receptor stimulation. Science. 1999;284:162-6 pubmed
    ..Autophosphorylation of CaMKII indirectly prolongs its PSD localization by increasing the calmodulin-binding affinity. ..
  5. Houston C, Lee H, Hosie A, Moss S, Smart T. Identification of the sites for CaMK-II-dependent phosphorylation of GABA(A) receptors. J Biol Chem. 2007;282:17855-65 pubmed
    ..These findings were confirmed in a neuronal environment by expressing recombinant GABA(A) receptors in cerebellar granule neurons. ..
  6. Gao Y, Tatavarty V, Korza G, Levin M, Carson J. Multiplexed dendritic targeting of alpha calcium calmodulin-dependent protein kinase II, neurogranin, and activity-regulated cytoskeleton-associated protein RNAs by the A2 pathway. Mol Biol Cell. 2008;19:2311-27 pubmed publisher
    ..Multiplexed dendritic targeting of different RNAs by the same pathway represents a new organizing principle for coordinating gene expression at the synapse. ..
  7. Kojundzic S, Puljak L, Hogan Q, Sapunar D. Depression of Ca(2+)/calmodulin-dependent protein kinase II in dorsal root ganglion neurons after spinal nerve ligation. J Comp Neurol. 2010;518:64-74 pubmed publisher
    ..These results indicate that diminished afferent activity after axotomy may lead to decreased phosphorylation of CaMKIIalpha. ..
  8. Stack E, Desarnaud F, Siwek D, Datta S. A novel role for calcium/calmodulin kinase II within the brainstem pedunculopontine tegmentum for the regulation of wakefulness and rapid eye movement sleep. J Neurochem. 2010;112:271-81 pubmed publisher
  9. Moriguchi S, Oomura Y, Shioda N, Han F, Hori N, Aou S, et al. Ca2+/calmodulin-dependent protein kinase II and protein kinase C activities mediate extracellular glucose-regulated hippocampal synaptic efficacy. Mol Cell Neurosci. 2011;46:101-7 pubmed publisher
    ..Taken together, CaMKII and PKC activation likely mediate potentiation of fEPSPs by elevated glucose levels, and CaMKII activity is also associated with LTP induction in the hippocampal CA1 region. ..
  10. Lisman J, Yasuda R, Raghavachari S. Mechanisms of CaMKII action in long-term potentiation. Nat Rev Neurosci. 2012;13:169-82 pubmed publisher
    ..These processes are all localized to stimulated spines and account for the synapse-specificity of LTP. In the later stages of LTP, CaMKII has a structural role in enlarging and strengthening the synapse. ..
  11. Marsden K, Shemesh A, Bayer K, Carroll R. Selective translocation of Ca2+/calmodulin protein kinase IIalpha (CaMKIIalpha) to inhibitory synapses. Proc Natl Acad Sci U S A. 2010;107:20559-64 pubmed publisher
    ..This preferential targeting of CaMKII? to glutamatergic or GABAergic synapses provides neurons with a mechanism whereby activity can selectively potentiate excitation or inhibition through a single kinase mediator. ..
  12. Opazo P, Labrecque S, Tigaret C, Frouin A, Wiseman P, De Koninck P, et al. CaMKII triggers the diffusional trapping of surface AMPARs through phosphorylation of stargazin. Neuron. 2010;67:239-52 pubmed publisher
    ..Thus, NMDA-dependent Ca(2+) influx in the post-synapse triggers a CaMKII- and Stargazin-dependent decrease in AMPAR diffusional exchange at synapses that controls synaptic function...
  13. Fan W, Li X, Cooper N. CaMKIIalphaB mediates a survival response in retinal ganglion cells subjected to a glutamate stimulus. Invest Ophthalmol Vis Sci. 2007;48:3854-63 pubmed
    ..In response to the glutamate stimulus, the expression of survival genes such as BDNF may be enhanced through elevation of this particular isoform of the CaMKIIalpha gene. ..
  14. Carlton S. Localization of CaMKIIalpha in rat primary sensory neurons: increase in inflammation. Brain Res. 2002;947:252-9 pubmed
  15. Osuka K, Watanabe Y, Usuda N, Nakazawa A, Fukunaga K, Miyamoto E, et al. Phosphorylation of neuronal nitric oxide synthase at Ser847 by CaM-KII in the hippocampus of rat brain after transient forebrain ischemia. J Cereb Blood Flow Metab. 2002;22:1098-106 pubmed
  16. Illario M, Cavallo A, Bayer K, Di Matola T, Fenzi G, Rossi G, et al. Calcium/calmodulin-dependent protein kinase II binds to Raf-1 and modulates integrin-stimulated ERK activation. J Biol Chem. 2003;278:45101-8 pubmed
    ..These findings also provide evidence supporting the possible existence of cross-talk between other intracellular pathways involving CaMKII and Raf-1. ..
  17. Fujii H, Inoue M, Okuno H, Sano Y, Takemoto Kimura S, Kitamura K, et al. Nonlinear decoding and asymmetric representation of neuronal input information by CaMKII? and calcineurin. Cell Rep. 2013;3:978-87 pubmed publisher
    ..These results provide evidence that CaMKII? and calcineurin are fine-tuned to unique bandwidths and compute input variables in an asymmetric manner. ..
  18. Pi H, Otmakhov N, El Gaamouch F, Lemelin D, De Koninck P, Lisman J. CaMKII control of spine size and synaptic strength: role of phosphorylation states and nonenzymatic action. Proc Natl Acad Sci U S A. 2010;107:14437-42 pubmed publisher
    ..This form fails to enhance synaptic strength but increases spine size, presumably by a structural process. Thus very different mechanisms govern how CaMKII affects spine structure and synaptic function. ..
  19. Fink C, Bayer K, Myers J, Ferrell J, Schulman H, Meyer T. Selective regulation of neurite extension and synapse formation by the beta but not the alpha isoform of CaMKII. Neuron. 2003;39:283-97 pubmed
  20. Wang C, Li N, Liu X, Zheng Y, Cao X. A novel endogenous human CaMKII inhibitory protein suppresses tumor growth by inducing cell cycle arrest via p27 stabilization. J Biol Chem. 2008;283:11565-74 pubmed publisher
  21. Robison A, Bass M, Jiao Y, MacMillan L, Carmody L, Bartlett R, et al. Multivalent interactions of calcium/calmodulin-dependent protein kinase II with the postsynaptic density proteins NR2B, densin-180, and alpha-actinin-2. J Biol Chem. 2005;280:35329-36 pubmed
  22. Du F, Saitoh F, Tian Q, Miyazawa S, Endo S, Suzuki T. Mechanisms for association of Ca2+/calmodulin-dependent protein kinase II with lipid rafts. Biochem Biophys Res Commun. 2006;347:814-20 pubmed
    ..a. 261-309, 371-420, and 421-478). The multimeric structure of the full-length molecule also appeared to contribute to efficient lipid raft-targeting. Acylation of CaMKIIalpha did not appear to be a mechanism for the targeting. ..
  23. Feng B, Raghavachari S, Lisman J. Quantitative estimates of the cytoplasmic, PSD, and NMDAR-bound pools of CaMKII in dendritic spines. Brain Res. 2011;1419:46-52 pubmed publisher
    ..Of particular note, the finding that the CaMKII signal in spines shows only transient activation (open state) after LTP induction is subject to the qualification that it does not reflect the small but important pool bound to the NMDAR. ..
  24. Holmfeldt P, Zhang X, Stenmark S, Walczak C, Gullberg M. CaMKIIgamma-mediated inactivation of the Kin I kinesin MCAK is essential for bipolar spindle formation. EMBO J. 2005;24:1256-66 pubmed
    ..These two mechanisms, involving CaMKIIgamma and TOGp, respectively, are both essential for spindle bipolarity in a normal physiological context, but not in MCAK-depleted cells. ..
  25. Liu W, Chang L, Song Y, Gao X, Ling W, Lu T, et al. Immunolocalization of CaMKII and NR2B in hippocampal subregions of rat during postnatal development. Acta Histochem. 2013;115:264-72 pubmed publisher
    ..Discovery of the alteration of the relationship between expression of CaMKII and NMDAR subunits may be helpful for understanding mechanisms and therapy of neurodegenerative diseases. ..
  26. Maeda N, Toku S, Naito Y, Nishiura H, Tanaka T, Yamamoto H. Phosphorylation of ribosomal protein S19 at Ser59 by CaM kinase I alpha. J Neurochem. 2009;109:393-402 pubmed publisher
    ..These results suggest that CaM kinase Ialpha regulates the functions of RPS19 through phosphorylation of Ser59. ..
  27. Caffino L, Cassina C, Giannotti G, Orru A, Moro F, Di Clemente A, et al. Short-term abstinence from cocaine self-administration, but not passive cocaine infusion, elevates ?CaMKII autophosphorylation in the rat nucleus accumbens and medial prefrontal cortex. Int J Neuropsychopharmacol. 2014;17:323-9 pubmed publisher
    ..The persistent enhancement in the mPFC of abstinent rats may represent a previously unappreciated contribution to initial incubation of cocaine-seeking. ..
  28. Matsumoto S, Shamloo M, Isshiki A, Wieloch T. Persistent phosphorylation of synaptic proteins following middle cerebral artery occlusion. J Cereb Blood Flow Metab. 2002;22:1107-13 pubmed
  29. Skelding K, Spratt N, Fluechter L, Dickson P, Rostas J. ?CaMKII is differentially regulated in brain regions that exhibit differing sensitivities to ischemia and excitotoxicity. J Cereb Blood Flow Metab. 2012;32:2181-92 pubmed publisher
    ..These results implicate intrinsic tissue differences in Thr253-?CaMKII phosphorylation in the differential sensitivities of brain regions to ischemia/excitotoxicity. ..
  30. Krapivinsky G, Medina I, Krapivinsky L, Gapon S, Clapham D. SynGAP-MUPP1-CaMKII synaptic complexes regulate p38 MAP kinase activity and NMDA receptor-dependent synaptic AMPA receptor potentiation. Neuron. 2004;43:563-74 pubmed
    ..siRNA-mediated SynGAP knockdown confirmed these results. These data implicate SynGAP in NMDAR- and CaMKII-dependent regulation of AMPAR trafficking. ..
  31. Gardner O, Shiau C, Chen C, Graves L. Peroxisome proliferator-activated receptor gamma-independent activation of p38 MAPK by thiazolidinediones involves calcium/calmodulin-dependent protein kinase II and protein kinase R: correlation with endoplasmic reticulum stress. J Biol Chem. 2005;280:10109-18 pubmed
    ..Furthermore, using structural derivatives of TZDs that lack PPARgamma ligand-binding activity as well as a PPARgamma antagonist, we show that activation of these kinase signaling pathways is PPARgamma-independent. ..
  32. Tran L, Keele N. CaMKIIα knockdown decreases anxiety in the open field and low serotonin-induced upregulation of GluA1 in the basolateral amygdala. Behav Brain Res. 2016;303:152-9 pubmed publisher
    ..Our results suggest that the CaMKII signaling plays a key role in low 5-HT-induced anxiety and mood disturbances, potentially through regulation of GluA1 expression in the BLA. ..
  33. Mori Y, Imaizumi K, Katayama T, Yoneda T, Tohyama M. Two cis-acting elements in the 3' untranslated region of alpha-CaMKII regulate its dendritic targeting. Nat Neurosci. 2000;3:1079-84 pubmed
    ..This inhibition was removed in depolarized neurons, and such activity-dependent derepression was a primary requirement for their dendritic targeting. ..
  34. Kang J, Wei X, Liu J, Wong Riley M, Ju G, Liu Y. Expression of phospho-Ca(2+) /calmodulin-dependent protein kinase II in the pre-Bötzinger complex of rats. J Neurochem. 2013;126:349-59 pubmed publisher
    ..In somas, CaMKII acts on both symmetric and asymmetric synapses, mediating excitatory and inhibitory synaptic transmission. P-CaMKII was also localized to the perisynaptic and extrasynaptic regions in the pre-BötC. ..
  35. Kamata A, Takeuchi Y, Fukunaga K. Identification of the isoforms of Ca2+/calmodulin-dependent protein kinase II and expression of brain-derived neurotrophic factor mRNAs in the substantia nigra. J Neurochem. 2006;96:195-203 pubmed
    ..Taken together with our previous observations, the results suggest that the CaMKIIdelta3 isoform is involved in the expression of BDNF in the SN. ..
  36. da Silva W, Cardoso G, Bonini J, Benetti F, Izquierdo I. Memory reconsolidation and its maintenance depend on L-voltage-dependent calcium channels and CaMKII functions regulating protein turnover in the hippocampus. Proc Natl Acad Sci U S A. 2013;110:6566-70 pubmed publisher
  37. Wei W, Dong J, Liu W, Wang Y, Chen J. [Effect of iodine deficiency and hypothyroidism on the protein expressions of CaMK II in the hippocampus of pups]. Wei Sheng Yan Jiu. 2010;39:180-3 pubmed
    ..74 +/- 3.33) and 15 mg/L groups (26.89 +/- 5.25) were significantly lower than those of controls(40.53 +/- 3.65), P < 0.05. Iodine deficiency and hypothyroidism may decrease the protein expression of CaMK II. ..
  38. Boric M, Jelicic Kadic A, Puljak L. The expression of calcium/calmodulin-dependent protein kinase II in the dorsal horns of rats with type 1 and type 2 diabetes. Neurosci Lett. 2014;579:151-6 pubmed publisher
    ..These results suggest a potential role for CaMKII in diabetic neuropathy development. Inhibition of CaMKII signaling pathways should be further explored as a potential treatment target in painful diabetic neuropathy. ..
  39. Sun H, Wu H, Liu J, Wen J, Zhu Z, Li H. Prenatal Stress Impairs Spatial Learning and Memory Associated with Lower mRNA Level of the CAMKII and CREB in the Adult Female Rat Hippocampus. Neurochem Res. 2017;42:1496-1503 pubmed publisher
    ..Our findings suggested that CaMKII and CREB may be involved in spatial learning and memory processes in the prenatally stressed adult female offspring. ..
  40. Lu H, MacGillavry H, Frost N, Blanpied T. Multiple spatial and kinetic subpopulations of CaMKII in spines and dendrites as resolved by single-molecule tracking PALM. J Neurosci. 2014;34:7600-10 pubmed publisher
  41. Ramarao G, Waghmare C, Srivastava N, Bhattacharya B. Regional alterations of JNK3 and CaMKII? subunit expression in the rat brain after soman poisoning. Hum Exp Toxicol. 2011;30:448-59 pubmed publisher
    ..CaMKII activity was increased in cerebrum and decreased in cerebellum. Results suggest that altered expression of both the protein kinases play a role in nerve agent-induced long-term neurotoxic effects. ..
  42. Pufall M, Lee G, Nelson M, Kang H, Velyvis A, Kay L, et al. Variable control of Ets-1 DNA binding by multiple phosphates in an unstructured region. Science. 2005;309:142-5 pubmed
    ..Variable phosphorylation thus serves as a "rheostat" for cell signaling to fine-tune transcription at the level of DNA binding. ..
  43. Mizutani A, Kuroda Y, Futatsugi A, Furuichi T, Mikoshiba K. Phosphorylation of Homer3 by calcium/calmodulin-dependent kinase II regulates a coupling state of its target molecules in Purkinje cells. J Neurosci. 2008;28:5369-82 pubmed publisher
  44. Grant P, Best S, Sanmugalingam N, Alessio R, Jama A, Torok K. A two-state model for Ca2+/CaM-dependent protein kinase II (alphaCaMKII) in response to persistent Ca2+ stimulation in hippocampal neurons. Cell Calcium. 2008;44:465-78 pubmed publisher
    ..Punctate deposition disables both the interactions and the activity of CaMKII. ..
  45. Gökçek Saraç Ç, Adali O, Jakubowska Doğru E. Hippocampal levels of ChAT, PKA, phospho-PKA and phospho-CaMKII? but not CaMKII? positively correlate with spatial learning skills in rats. Neurosci Lett. 2013;545:112-6 pubmed publisher
  46. Song B, Meng F, Yan X, Guo J, Zhang G. Cerebral ischemia immediately increases serine phosphorylation of the synaptic RAS-GTPase activating protein SynGAP by calcium/calmodulin-dependent protein kinase II alpha in hippocampus of rats. Neurosci Lett. 2003;349:183-6 pubmed
  47. Liu S, Fa M, Ninan I, Trinchese F, Dauer W, Arancio O. Alpha-synuclein involvement in hippocampal synaptic plasticity: role of NO, cGMP, cGK and CaMKII. Eur J Neurosci. 2007;25:3583-96 pubmed
    ..Thus, our results suggest that NO, cGMP, GMP-dependent protein kinase and calmodulin-dependent protein kinase II play a key role in the redistribution of alpha-synuclein during plasticity. ..
  48. Ishiguro K, Ando T, Goto H, Xavier R. Bcl10 is phosphorylated on Ser138 by Ca2+/calmodulin-dependent protein kinase II. Mol Immunol. 2007;44:2095-100 pubmed
    ..These findings suggest that CaMKII modulates NF-kappaB activation via phosphorylating Bcl10 as well as Carma1. ..
  49. Thiel G, Czernik A, Gorelick F, Nairn A, Greengard P. Ca2+/calmodulin-dependent protein kinase II: identification of threonine-286 as the autophosphorylation site in the alpha subunit associated with the generation of Ca2+-independent activity. Proc Natl Acad Sci U S A. 1988;85:6337-41 pubmed
    ..The sequences obtained for two phosphopeptides derived from secondary chymotryptic digestion of CB-1 confirmed that Thr-286 was the phosphorylated residue. ..
  50. Dupuis J, Ladépêche L, Seth H, Bard L, VARELA J, Mikasova L, et al. Surface dynamics of GluN2B-NMDA receptors controls plasticity of maturing glutamate synapses. EMBO J. 2014;33:842-61 pubmed publisher
    ..We thus uncover a non-canonical mechanism by which GluN2B-NMDAR surface dynamics plays a critical role in the plasticity of maturing synapses through a direct interplay with CaMKII. ..
  51. Hinds H, Goussakov I, Nakazawa K, Tonegawa S, Bolshakov V. Essential function of alpha-calcium/calmodulin-dependent protein kinase II in neurotransmitter release at a glutamatergic central synapse. Proc Natl Acad Sci U S A. 2003;100:4275-80 pubmed
  52. Xue J, Li G, Bharucha E, Cooper N. Developmentally regulated expression of CaMKII and iGluRs in the rat retina. Brain Res Dev Brain Res. 2002;138:61-70 pubmed
    ..The temporal differences in subunit expression of these synaptically relevant molecules suggest that they play distinct roles during the development of the retina. ..
  53. Boric M, Jelicic Kadic A, Puljak L. Cutaneous expression of calcium/calmodulin-dependent protein kinase II in rats with type 1 and type 2 diabetes. J Chem Neuroanat. 2014;61-62:140-6 pubmed publisher
    ..Further research on physiological role of CaMKII in skin and its role in cutaneous diabetic complications should be undertaken in order to elucidate its function in epidermis. ..