Genomes and Genes
Gene Symbol: Camk2d
Description: calcium/calmodulin-dependent protein kinase II delta
Alias: CAMK1, Camk2, Camki, RATCAMKI, calcium/calmodulin-dependent protein kinase type II subunit delta, Ca++/calmodulin-dependent protein kinase 2 delta subunit, Ca++/calmodulin-dependent protein kinase II, delta subunit, caM kinase II subunit delta, caM-kinase II delta chain, caMK-II subunit delta, calcium/calmodulin-dependent protein kinase (CaM kinase) II delta, calcium/calmodulin-dependent protein kinase type II delta chain
- Cohen T, Waddell D, Barrientos T, Lu Z, Feng G, Cox G, et al. The histone deacetylase HDAC4 connects neural activity to muscle transcriptional reprogramming. J Biol Chem. 2007;282:33752-9 pubmed..Our findings establish HDAC4 as a neural activity-regulated deacetylase and a key signaling component that relays neural activity to the muscle transcriptional machinery. ..
- House S, Ginnan R, Armstrong S, Singer H. Calcium/calmodulin-dependent protein kinase II-delta isoform regulation of vascular smooth muscle cell proliferation. Am J Physiol Cell Physiol. 2007;292:C2276-87 pubmed..These results indicate that CaMKIIdelta(2) is specifically induced during modulation of VSM cells to the synthetic phenotypic and is a positive regulator of serum-stimulated proliferation. ..
- Fang L, Wu J, Zhang X, Lin Q, Willis W. Calcium/calmodulin dependent protein kinase II regulates the phosphorylation of cyclic AMP-responsive element-binding protein of spinal cord in rats following noxious stimulation. Neurosci Lett. 2005;374:1-4 pubmed..These results suggest that increased phosphorylation of CREB protein may contribute to central sensitization following acute peripheral noxious stimuli, and the effect may be regulated through the activation of CaM kinase cascades. ..
- Pfleiderer P, Lu K, Crow M, Keller R, Singer H. Modulation of vascular smooth muscle cell migration by calcium/ calmodulin-dependent protein kinase II-delta 2. Am J Physiol Cell Physiol. 2004;286:C1238-45 pubmed..An inclusive interpretation of results using both pharmacological and molecular approaches raises the hypothesis that CaMKII delta(2) autophosphorylation may play an important role in PDGF-stimulated VSM cell migration. ..
- Zhang T, Maier L, Dalton N, Miyamoto S, Ross J, Bers D, et al. The deltaC isoform of CaMKII is activated in cardiac hypertrophy and induces dilated cardiomyopathy and heart failure. Circ Res. 2003;92:912-9 pubmed
- Hamdani N, Krysiak J, Kreusser M, Neef S, dos Remedios C, Maier L, et al. Crucial role for Ca2(+)/calmodulin-dependent protein kinase-II in regulating diastolic stress of normal and failing hearts via titin phosphorylation. Circ Res. 2013;112:664-74 pubmed publisher..CaMKII phosphorylates the titin springs at conserved serines/threonines, thereby lowering F(passive). Deranged CaMKII-dependent titin phosphorylation occurs in heart failure and contributes to altered diastolic stress. ..
- Coultrap S, Bayer K. CaMKII regulation in information processing and storage. Trends Neurosci. 2012;35:607-18 pubmed publisher..Recent findings also implicate CaMKII in long-term depression (LTD), as well as functional roles at inhibitory synapses, lending renewed emphasis on better understanding the spatiotemporal control of CaMKII regulation. ..
- Liu Y, Spinelli A, Sun L, Jiang M, Singer D, Ginnan R, et al. MicroRNA-30 inhibits neointimal hyperplasia by targeting Ca(2+)/calmodulin-dependent protein kinase IIÎ´ (CaMKIIÎ´). Sci Rep. 2016;6:26166 pubmed publisher..These studies define a novel mechanism for regulating CaMKIIÎ´ expression in VSM and provide a new potential therapeutic strategy to reduce progression of vascular proliferative diseases, including atherosclerosis and restenosis. ..
- Maier L, Zhang T, Chen L, DeSantiago J, Brown J, Bers D. Transgenic CaMKIIdeltaC overexpression uniquely alters cardiac myocyte Ca2+ handling: reduced SR Ca2+ load and activated SR Ca2+ release. Circ Res. 2003;92:904-11 pubmed..We conclude that CaMKIIdeltaC overexpression causes acute modulation of excitation-contraction coupling, which contributes to heart failure. ..
- Ginnan R, Sun L, Schwarz J, Singer H. MEF2 is regulated by CaMKII?2 and a HDAC4-HDAC5 heterodimer in vascular smooth muscle cells. Biochem J. 2012;444:105-14 pubmed publisher..Taken together, these results illustrate a mechanism by which CaMKII?(2) mediates MEF2-dependent gene transcription in VSMCs through regulation of HDAC4 and HDAC5. ..
- Xu X, Yang D, Ding J, Wang W, Chu P, Dalton N, et al. ASF/SF2-regulated CaMKIIdelta alternative splicing temporally reprograms excitation-contraction coupling in cardiac muscle. Cell. 2005;120:59-72 pubmed..Our results validate ASF/SF2 as a fundamental splicing regulator in the reprogramming pathway and reveal the central contribution of ASF/SF2-regulated CaMKIIdelta alternative splicing to functional remodeling in developing heart. ..
- Mayer P, Mohlig M, Idlibe D, Pfeiffer A. Novel and uncommon isoforms of the calcium sensing enzyme calcium/calmodulin dependent protein kinase II in heart tissue. Basic Res Cardiol. 1995;90:372-9 pubmed..Such compounds would act similarly to but much more selectively than digitalis glycosides and would be likely to possess less side effects. ..
- Yao L, Fan P, Jiang Z, Viatchenko Karpinski S, Wu Y, Kornyeyev D, et al. Nav1.5-dependent persistent Na+ influx activates CaMKII in rat ventricular myocytes and N1325S mice. Am J Physiol Cell Physiol. 2011;301:C577-86 pubmed publisher..5, further promoting Na(+) influx. Pharmacological inhibition of either CaMKII or Na(v)1.5 can ameliorate cardiac dysfunction caused by excessive Na(+) influx. ..
- Cha M, Jang J, Ham O, Song B, Lee S, Lee C, et al. MicroRNA-145 suppresses ROS-induced Ca2+ overload of cardiomyocytes by targeting CaMKII?. Biochem Biophys Res Commun. 2013;435:720-6 pubmed publisher..This study demonstrates that miR-145 regulates reactive oxygen species (ROS)-induced Ca(2+) overload in cardiomyocytes. Thus, miR-145 affects ROS-mediated gene regulation and cellular injury responses. ..
- Afroze T, Yang L, Wang C, Gros R, Kalair W, Hoque A, et al. Calcineurin-independent regulation of plasma membrane Ca2+ ATPase-4 in the vascular smooth muscle cell cycle. Am J Physiol Cell Physiol. 2003;285:C88-95 pubmed..These data show that G1/S-specific PMCA4 repression in proliferating VSMC is brought about by c-Myb and CaMK-II and that calcineurin may regulate cell cycle-associated [Ca2+]i through alternate targets. ..
- Schworer C, Rothblum L, Thekkumkara T, Singer H. Identification of novel isoforms of the delta subunit of Ca2+/calmodulin-dependent protein kinase II. Differential expression in rat brain and aorta. J Biol Chem. 1993;268:14443-9 pubmed..Reverse-transcription PCR analysis of additional rat tissues indicated that alternatively spliced variants of the delta subunit of Ca2+/calmodulin-dependent protein kinase II are expressed in a tissue-specific pattern. ..
- Szobi A, Rajtik T, Carnická S, Ravingerová T, Adameova A. Mitigation of postischemic cardiac contractile dysfunction by CaMKII inhibition: effects on programmed necrotic and apoptotic cell death. Mol Cell Biochem. 2014;388:269-76 pubmed publisher..Phosphorylation of CaMKII seems unlikely to determine the degree of postischemic recovery of contractile function. ..
- Yang D, Zhu W, Xiao B, Brochet D, Chen S, Lakatta E, et al. Ca2+/calmodulin kinase II-dependent phosphorylation of ryanodine receptors suppresses Ca2+ sparks and Ca2+ waves in cardiac myocytes. Circ Res. 2007;100:399-407 pubmed
- He J, Jiang S, Li F, Zhao X, Chu E, Sun M, et al. MicroRNA-30b-5p is involved in the regulation of cardiac hypertrophy by targeting CaMKII?. J Investig Med. 2013;61:604-12 pubmed publisher..Our study demonstrates that the expression of miR-30b-5p is down-regulated in cardiac hypertrophy, and restoration of its function inhibits the expression of CaMKII?, suggesting that miR-30b-5p may act as a hypertrophic suppressor. ..
- Ma Y, Cheng W, Wu S, Wong T. Oestrogen confers cardioprotection by suppressing Ca2+/calmodulin-dependent protein kinase II. Br J Pharmacol. 2009;157:705-15 pubmed publisher..Oestrogen confers cardioprotection at least partly by suppressing CaMKIIdelta. This effect of oestrogen on CaMKII is independent of the beta-adrenoceptor and occurs in addition to down-regulation of the receptor. ..
- Liu Y, Templeton D. Involvement of CaMK-II? and gelsolin in Cd(2+) -dependent cytoskeletal effects in mesangial cells. J Cell Physiol. 2013;228:78-86 pubmed publisher..We conclude that cytoskeletal effects of Cd in mesangial cells are partially mediated by Cd-dependent activation of CaMK-II?, binding of CaMK-II? and gelsolin to actin filaments, and cleavage of gelsolin. ..
- Mayadevi M, Praseeda M, Kumar K, Omkumar R. Sequence determinants on the NR2A and NR2B subunits of NMDA receptor responsible for specificity of phosphorylation by CaMKII. Biochim Biophys Acta. 2002;1598:40-5 pubmed..However, CaMKII shows decreased affinity towards the closely related NR2A subunit due to an -Ile-Asn- motif present as a natural insertion in the analogous sequence on NR2A. ..
- Li C, Cai X, Sun H, Bai T, Zheng X, Zhou X, et al. The ?A isoform of calmodulin kinase II mediates pathological cardiac hypertrophy by interfering with the HDAC4-MEF2 signaling pathway. Biochem Biophys Res Commun. 2011;409:125-30 pubmed publisher..These results provide new evidence for selective interfering cardiac hypertrophy and heart failure when CaMKII is considered as a therapeutic target. ..
- De Felice F, Vieira M, Bomfim T, Decker H, Velasco P, Lambert M, et al. Protection of synapses against Alzheimer's-linked toxins: insulin signaling prevents the pathogenic binding of Abeta oligomers. Proc Natl Acad Sci U S A. 2009;106:1971-6 pubmed publisher..The finding that synapse vulnerability to ADDLs can be mitigated by insulin suggests that bolstering brain insulin signaling, which can decline with aging and diabetes, could have significant potential to slow or deter AD pathogenesis. ..
- Mishra Gorur K, Singer H, Castellot J. The S18 ribosomal protein is a putative substrate for Ca2+/calmodulin-activated protein kinase II. J Biol Chem. 2002;277:33537-40 pubmed..Taken together these data support the idea that S18 could be a novel substrate for CaMK II, thus providing a potential link between Ca(2+)-mobilizing agents and protein translation. ..
- Rellos P, Pike A, Niesen F, Salah E, Lee W, von Delft F, et al. Structure of the CaMKIIdelta/calmodulin complex reveals the molecular mechanism of CaMKII kinase activation. PLoS Biol. 2010;8:e1000426 pubmed publisher..Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the Web plugin are available in Text S1. ..
- Takeuchi Y, Yamamoto H, Matsumoto K, Kimura T, Katsuragi S, Miyakawa T, et al. Nuclear localization of the delta subunit of Ca2+/calmodulin-dependent protein kinase II in rat cerebellar granule cells. J Neurochem. 1999;72:815-25 pubmed..Immunohistochemical study suggested the existence of these isoforms in the nuclei in cerebellar granule cells. These results suggest that CaM kinase IIdelta3 isoforms are involved in nuclear Ca2+ signaling in cerebellar granule cells. ..
- Ginnan R, Zou X, Pfleiderer P, Mercure M, Barroso M, Singer H. Vascular smooth muscle cell motility is mediated by a physical and functional interaction of Ca2+/calmodulin-dependent protein kinase II?2 and Fyn. J Biol Chem. 2013;288:29703-12 pubmed publisher..Taken together, these data demonstrate a dynamic interaction between CaMKII?2 and Fyn in VSM cells and indicate a mechanism by which CaMKII?2 and Fyn may coordinately regulate VSM cell motility. ..
- Bell J, Raaijmakers A, Curl C, Reichelt M, Harding T, Bei A, et al. Cardiac CaMKIIÎ´ splice variants exhibit target signaling specificity and confer sex-selective arrhythmogenic actions in the ischemic-reperfused heart. Int J Cardiol. 2015;181:288-96 pubmed publisher..Collectively these findings indicate that therapeutic approaches based on selective CaMKII splice form targeting may have potential benefit, and that sex-selective CaMKII intervention strategies may be valid. ..
- Chang H, Sheng J, Zhang L, Yue Z, Jiao B, Li J, et al. ROS-Induced Nuclear Translocation of Calpain-2 Facilitates Cardiomyocyte Apoptosis in Tail-Suspended Rats. J Cell Biochem. 2015;116:2258-69 pubmed publisher..Therefore, calpain-2 may represent a potentially therapeutic target for prevention of oxidative stress-associated cardiomyocyte apoptosis. ..
- Ashpole N, Herren A, Ginsburg K, Brogan J, Johnson D, Cummins T, et al. Ca2+/calmodulin-dependent protein kinase II (CaMKII) regulates cardiac sodium channel NaV1.5 gating by multiple phosphorylation sites. J Biol Chem. 2012;287:19856-69 pubmed publisher..5 at multiple sites (including Thr-594 and Ser-516) appears to be required to evoke loss-of-function changes in gating that could contribute to acquired Brugada syndrome-like effects in heart failure. ..
- Fluck M, Booth F, Waxham M. Skeletal muscle CaMKII enriches in nuclei and phosphorylates myogenic factor SRF at multiple sites. Biochem Biophys Res Commun. 2000;270:488-94 pubmed..The location of Thr-160 in the 3-D structure of SRF suggests that its phosphorylation by nuclear CaMKII may directly influence DNA binding of SRF and other MADS box factors. ..
- Little G, Bai Y, Williams T, Poizat C. Nuclear calcium/calmodulin-dependent protein kinase IIdelta preferentially transmits signals to histone deacetylase 4 in cardiac cells. J Biol Chem. 2007;282:7219-31 pubmed..previous studies in skeletal muscle cells have shown that HDAC4 lacking serine 246 cannot be phosphorylated by CaMKI/IV, a similar mutant is still phosphorylated by CaMKIIdeltaB...
- Qin Y, Zhang Z, Chen J, Ding X, Tong S, Song Z. Ca²? disorder caused by rapid electrical field stimulation can be modulated by CaMKII? expression in primary rat atrial myocytes. Biochem Biophys Res Commun. 2011;409:287-92 pubmed publisher..These results revealed the important role of CaMKII? in Ca(2+) disorder caused by electrical field stimulation. It also provided a potential method to improve Ca(2+) disorder in AF by modulating CaMKII? expression level. ..
- Lin C, Lee I, Wu W, Liu C, Hsieh H, Hsiao L, et al. Thrombin mediates migration of rat brain astrocytes via PLC, Ca²?, CaMKII, PKC?, and AP-1-dependent matrix metalloproteinase-9 expression. Mol Neurobiol. 2013;48:616-30 pubmed publisher..These results concluded that thrombin activated a PLC/Ca(2+)/CaMKII/PKC?/p42/p44 MAPK and JNK1/2 pathway, which in turn triggered AP-1 activation and ultimately induced MMP-9 expression in RBA-1 cells. ..
- Ellis J, Valencia T, Zeng H, Roberts L, Deaton R, Grant S. CaM kinase IIdeltaC phosphorylation of 14-3-3beta in vascular smooth muscle cells: activation of class II HDAC repression. Mol Cell Biochem. 2003;242:153-61 pubmed
- Ji Y, Guo X, Zhang Z, Huang Z, Zhu J, Chen Q, et al. CaMKIIδ meditates phenylephrine induced cardiomyocyte hypertrophy through store-operated Ca2+ entry. Cardiovasc Pathol. 2017;27:9-17 pubmed publisher..In conclusion, these studies reveal that up-regulation of CaMKIIδ may contribute to the PE-induced myocardial hypertrophy through the activation of SOCE expressed in the cardiomyocytes. ..
- Deng A, Dene H, Rapp J. Mapping of a quantitative trait locus for blood pressure on rat chromosome 2. J Clin Invest. 1994;94:431-6 pubmed..The LOD score for existence of this blood pressure QTL based on the combined populations (n = 330) was 5.66 and accounted for 9.2% of the total variance and 26% of the genetic variance. ..
- Wu G, Wang H, Yang J, Yang Y, Liu C, Jing L, et al. kappa-Opioid receptor stimulation inhibits augmentation of Ca(2+) transient and hypertrophy induced by isoprenaline in neonatal rat ventricular myocytes - Role of CaMKIIdelta(B). Eur J Pharmacol. 2008;595:52-7 pubmed publisher..These results suggest that the inhibitory effect of kappa-opioid receptor stimulation on beta(1)-adrenoceptor stimulation may also involve CaMKIIdelta. ..
- Balla Z, Hoch B, Karczewski P, Blasig I. Calcium/calmodulin-dependent protein kinase IIdelta 2 and gamma isoforms regulate potassium currents of rat brain capillary endothelial cells under hypoxic conditions. J Biol Chem. 2002;277:21306-14 pubmed..It is concluded that the activation of Ca2+/calmodulin-dependent protein kinase II decreases inactivation of the voltage-gated outward K+ current, thereby counteracting depolarization of the hypoxic endothelium. ..
- Hund T, Koval O, Li J, Wright P, Qian L, Snyder J, et al. A ?(IV)-spectrin/CaMKII signaling complex is essential for membrane excitability in mice. J Clin Invest. 2010;120:3508-19 pubmed publisher..Collectively, our data define an unexpected but indispensable molecular platform that determines membrane excitability in the mouse heart and brain. ..
- Deng A, Jackson C, Hoebee B, Rapp J. Mapping of rat chromosome 2 markers generated from chromosome-sorted DNA. Mamm Genome. 1997;8:731-5 pubmed..Combining new and existing markers, the marker density for the 30-cM region approaches, on average, one marker per 1.1 cM. ..
- Song Y, Cho H, Ryu S, Yoon J, Park S, Noh C, et al. L-type Ca(2+) channel facilitation mediated by H(2)O(2)-induced activation of CaMKII in rat ventricular myocytes. J Mol Cell Cardiol. 2010;48:773-80 pubmed publisher..In conclusion, oxidation-dependent facilitation of L-type Ca(2+) channels is mediated by oxidation-dependent CaMKII activation, in which local Ca(2+) increases induced by SR Ca(2+) release is required. ..
- Chang L, Zhang J, Tseng Y, Xie C, Ilany J, Bruning J, et al. Rad GTPase deficiency leads to cardiac hypertrophy. Circulation. 2007;116:2976-2983 pubmed publisher..The present study will have significant implications for understanding the mechanisms of cardiac hypertrophy and setting the basis for the development of new strategies for treatment of cardiac hypertrophy. ..
- Little G, Saw A, Bai Y, Dow J, Marjoram P, Simkhovich B, et al. Critical role of nuclear calcium/calmodulin-dependent protein kinase IIdeltaB in cardiomyocyte survival in cardiomyopathy. J Biol Chem. 2009;284:24857-68 pubmed publisher..These results suggest that selective targeting of CaMKII in the nuclear compartment might represent a strategy to regulate cardiac apoptosis and to reduce Dox-mediated cardiotoxicity. ..
- Aversa Z, Alamdari N, Castillero E, Muscaritoli M, Rossi Fanelli F, Hasselgren P. CaMKII activity is reduced in skeletal muscle during sepsis. J Cell Biochem. 2013;114:1294-305 pubmed publisher..Decreased phosphorylation (consistent with activation) of GSK-3? may be a consequence of reduced CaMKII activity, indicating that inhibited CaMKII activity may be involved in the catabolic response to sepsis. ..
- Zhang M, Shan H, Gu Z, Wang D, Wang T, Wang Z, et al. Increased expression of calcium/calmodulin-dependent protein kinase type II subunit ? after rat traumatic brain injury. J Mol Neurosci. 2012;46:631-43 pubmed publisher..However, the inherent mechanisms remained unknown. Further studies are needed to confirm the exact role of CaMKII? after brain injury. ..
- Jones R, JOURD HEUIL D, Salerno J, Smith S, Singer H. iNOS regulation by calcium/calmodulin-dependent protein kinase II in vascular smooth muscle. Am J Physiol Heart Circ Physiol. 2007;292:H2634-42 pubmed..The results suggest that CaMKIIdelta(2) may be an important regulator of iNOS trafficking and activity in VSMCs. ..