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Gene Review

CAMK1D  -  calcium/calmodulin-dependent protein...

Homo sapiens

Synonyms: CAMKID, CKLiK, CaM kinase I delta, CaM kinase ID, CaM-K1, ...
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Disease relevance of CAMK1D

  • CaM kinase signaling induces cardiac hypertrophy and activates the MEF2 transcription factor in vivo [1].
  • The caM kinase, Pnck, is spatially and temporally regulated during murine mammary gland development and may identify an epithelial cell subtype involved in breast cancer [2].
  • The human CaMKK, which was expressed as a Flag-tagged protein in human non-small cell lung cancer H- 1299 cells followed by immunoprecipitation with anti-Flag antibody, was shown to phosphorylate recombinant human CaMK I in a calcium/CaM-dependent fashion [3].
  • These results indicated that CaMK II regulates c-FLIP expression and phosphorylation, thus modulating Fas-mediated signaling in glioma cells [4].
  • METHODS: The previously unknown complete coding sequences of human CaMK IIbeta and the kinase domain of CaMK IIdelta were cloned from a human insulinoma cDNA library [5].

Psychiatry related information on CAMK1D

  • The present study correlated the increased locomotor activity following ischemic insult with alterations in CaM kinase mRNA levels and immunocytochemical labeling of alpha and beta CaM kinase subunits in the hippocampus [6].
  • In this review, we demonstrate the biologic behavior of seven novel molecules (Plks, Eph/ephrin, Id family, CaMK, c-Ets1, Elf-1, and survivin) in the endometrial carcinoma [7].

High impact information on CAMK1D

  • This pathway could provide an interface between the potentiation of Ca2+ signals by CaM kinase and longer-term modifications of neuronal gene expression [8].
  • Widespread localization, responsiveness to numerous signal transduction systems, and broad substrate specificity enable the multifunctional CaM kinase to mediate regulation of many cellular functions [8].
  • The initial P/Q-type calcium signal is amplified by release of calcium from intracellular stores and acts through phosphorylation that is dependent on the calmodulin-dependent kinase CaM K II/IV, protein kinase A and mitogen-activated protein kinase kinase [9].
  • The cAMP kinase incorporates one mol phosphate per mol of the 142K peptide and binding of (+)PN-200/110, a potent Ca antagonist, is allosterically affected by D-cis-diltiazem and verapamil [10].
  • Multifunctional calcium-calmodulin-dependent protein kinase (CaM kinase) transduces transient elevations in intracellular calcium into changes in the phosphorylation state and activity of target proteins [11].

Chemical compound and disease context of CAMK1D

  • We investigated the effects of cocaine, in concentrations commonly found in chronic cocaine users, on calcium/calmodulin kinase (CaMK), and whether cocaine can activate CaMK, increase cardiac myocyte protein expression, and cause cardiac hypertrophy in this manner [12].
  • The effects of immunosuppressants and inhibitors of specific calcium/calmodulin kinase (CaMK) of types II and IV on progestin/glucocorticosteroid-induced transcription were studied in two human stably transfected breast cancer T47D cell lines [13].

Biological context of CAMK1D


Anatomical context of CAMK1D


Associations of CAMK1D with chemical compounds

  • These data indicate a role for CaM kinase stimulation and resultant threonine phosphorylation of NMHC-IIA in RBL-2H3 m1 cell activation [20].
  • CaMK but not PKA signaling is suppressed by low concentrations of heparin [16].
  • Selective stimulation of CaMK with Ca(2+) ionophores and of PKA with forskolin or dibutyryl cAMP both result in induction of c-fos mRNA [16].
  • In series V and VI, cocaine effects on calcium currents (ICa) and intracellular Ca ([Ca]i) were determined before and after CaMK inhibition with KN-62 in rat myocytes [12].
  • Whereas CaMK inhibition affected neither integrin-stimulated Akt phosphorylation nor p21Ras or Mek-1 activity, it was necessary for Raf-1 activity [21].

Other interactions of CAMK1D

  • They also exhibit a distinct ability to undergo autophosphorylation and to phosphorylate the downstream kinases CaMK I and CaMK IV [22].
  • To determine which multifunctional CaMK acts in G(1), we expressed kinase-deficient forms of CaMKI and CaMKII [23].
  • Supporting this finding, CaM-K inhibition using KN-93 also resulted in a reduction of cyclin D1 protein and pRb phosphorylation when cells were compared with control cultures [24].
  • The calmodulin-dependent kinase (CaM-K) cascade, a Ca2+-triggered system involving phosphorylation and activation of CaM-KI and CaM-KIV by CaM kinase kinase (CaM-KK), regulates transcription through direct phosphorylation of transcription factors such as cAMP response element-binding protein [25].
  • The inhibitory effect of CaM-K II on IL-2 promoter was associated with decreased transcription of its AP-1 and NF-AT transactivating pathways [26].

Analytical, diagnostic and therapeutic context of CAMK1D

  • Molecular cloning and characterization of CLICK-III/CaMKIgamma, a novel membrane-anchored neuronal Ca2+/calmodulin-dependent protein kinase (CaMK) [27].
  • Novel (Rp)-cAMPS analogs as tools for inhibition of cAMP-kinase in cell culture. Basal cAMP-kinase activity modulates interleukin-1 beta action [28].
  • In series I to III, 0 (control) or cocaine in concentrations of 10 to 10 mol/L was added to cultured adult rat cardiac ventricular myocytes to determine by Western blots and by P incorporation the optimal treatment time and the optimal dose for CaMK activation [12].
  • In series IV we measured by silver staining beta-myosin heavy chain protein (beta-MHC) expression in myocytes before and after cocaine and also CaMK inhibition with KN-62 (1-[N,O-bis-(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine) [12].
  • Gel band shift assays and densitometry experiments with intact CaM kinase I and the CaM-binding domain peptide (CaMKIp) reveal that they bind in an analogous manner, giving rise to 1:1 complexes [29].


  1. CaM kinase signaling induces cardiac hypertrophy and activates the MEF2 transcription factor in vivo. Passier, R., Zeng, H., Frey, N., Naya, F.J., Nicol, R.L., McKinsey, T.A., Overbeek, P., Richardson, J.A., Grant, S.R., Olson, E.N. J. Clin. Invest. (2000) [Pubmed]
  2. The caM kinase, Pnck, is spatially and temporally regulated during murine mammary gland development and may identify an epithelial cell subtype involved in breast cancer. Gardner, H.P., Ha, S.I., Reynolds, C., Chodosh, L.A. Cancer Res. (2000) [Pubmed]
  3. Cloning, expression and chromosomal localization of human Ca2+/calmodulin-dependent protein kinase kinase. Hsu, L.S., Tsou, A.P., Chi, C.W., Lee, C.H., Chen, J.Y. J. Biomed. Sci. (1998) [Pubmed]
  4. Calcium/calmodulin-dependent protein kinase II regulation of c-FLIP expression and phosphorylation in modulation of Fas-mediated signaling in malignant glioma cells. Yang, B.F., Xiao, C., Roa, W.H., Krammer, P.H., Hao, C. J. Biol. Chem. (2003) [Pubmed]
  5. Cloning and quantitative determination of the human Ca2+/calmodulin-dependent protein kinase II (CaMK II) isoforms in human beta cells. Rochlitz, H., Voigt, A., Lankat-Buttgereit, B., Göke, B., Heimberg, H., Nauck, M.A., Schiemann, U., Schatz, H., Pfeiffer, A.F. Diabetologia (2000) [Pubmed]
  6. Transient cerebral ischemia decreases calcium/calmodulin-dependent protein kinase II immunoreactivity, but not mRNA levels in the gerbil hippocampus. Babcock, A.M., Liu, H., Paden, C.M., Edmo, D., Popper, P., Micevych, P.E. Brain Res. (1995) [Pubmed]
  7. The relationship between oncogene expression and clinical outcome in endometrial carcinoma. Takai, N., Ueda, T., Nishida, M., Nasu, K., Miyakawa, I. Current cancer drug targets. (2004) [Pubmed]
  8. Neuronal Ca2+/calmodulin-dependent protein kinases. Hanson, P.I., Schulman, H. Annu. Rev. Biochem. (1992) [Pubmed]
  9. P/Q-type calcium channels mediate the activity-dependent feedback of syntaxin-1A. Sutton, K.G., McRory, J.E., Guthrie, H., Murphy, T.H., Snutch, T.P. Nature (1999) [Pubmed]
  10. Purified dihydropyridine-binding site from skeletal muscle t-tubules is a functional calcium channel. Flockerzi, V., Oeken, H.J., Hofmann, F., Pelzer, D., Cavalié, A., Trautwein, W. Nature (1986) [Pubmed]
  11. Calmodulin trapping by calcium-calmodulin-dependent protein kinase. Meyer, T., Hanson, P.I., Stryer, L., Schulman, H. Science (1992) [Pubmed]
  12. Cocaine activates calcium/calmodulin kinase II and causes cardiomyocyte hypertrophy. Henning, R.J., Cuevas, J., Ivancsits, D., Sanchez, A. J. Cardiovasc. Pharmacol. (2006) [Pubmed]
  13. Calcium/calmodulin kinase inhibitors and immunosuppressant macrolides rapamycin and FK506 inhibit progestin- and glucocorticosteroid receptor-mediated transcription in human breast cancer T47D cells. Le Bihan, S., Marsaud, V., Mercier-Bodard, C., Baulieu, E.E., Mader, S., White, J.H., Renoir, J.M. Mol. Endocrinol. (1998) [Pubmed]
  14. Identification and characterization of CKLiK, a novel granulocyte Ca(++)/calmodulin-dependent kinase. Verploegen, S., Lammers, J.W., Koenderman, L., Coffer, P.J. Blood (2000) [Pubmed]
  15. Inhibition of neuronal nitric-oxide synthase by calcium/ calmodulin-dependent protein kinase IIalpha through Ser847 phosphorylation in NG108-15 neuronal cells. Komeima, K., Hayashi, Y., Naito, Y., Watanabe, Y. J. Biol. Chem. (2000) [Pubmed]
  16. Ca(2+)/calmodulin-dependent and cAMP-dependent kinases in induction of c-fos in human mesangial cells. Zeng, H., Liu, Y., Templeton, D.M. Am. J. Physiol. Renal Physiol. (2002) [Pubmed]
  17. Calmodulin-dependent kinase I regulates adrenal cell expression of aldosterone synthase. Condon, J.C., Pezzi, V., Drummond, B.M., Yin, S., Rainey, W.E. Endocrinology (2002) [Pubmed]
  18. Characterization of the role of CaMKI-like kinase (CKLiK) in human granulocyte function. Verploegen, S., Ulfman, L., van Deutekom, H.W., van Aalst, C., Honing, H., Lammers, J.W., Koenderman, L., Coffer, P.J. Blood (2005) [Pubmed]
  19. Phosphorylation of microtubule-associated protein tau: identification of the site for Ca2(+)-calmodulin dependent kinase and relationship with tau phosphorylation in Alzheimer tangles. Steiner, B., Mandelkow, E.M., Biernat, J., Gustke, N., Meyer, H.E., Schmidt, B., Mieskes, G., Söling, H.D., Drechsel, D., Kirschner, M.W. EMBO J. (1990) [Pubmed]
  20. Calcium-dependent threonine phosphorylation of nonmuscle myosin in stimulated RBL-2H3 mast cells. Buxton, D.B., Adelstein, R.S. J. Biol. Chem. (2000) [Pubmed]
  21. Calcium/calmodulin-dependent protein kinase II binds to Raf-1 and modulates integrin-stimulated ERK activation. Illario, M., Cavallo, A.L., Bayer, K.U., Di Matola, T., Fenzi, G., Rossi, G., Vitale, M. J. Biol. Chem. (2003) [Pubmed]
  22. Human Ca2+/calmodulin-dependent protein kinase kinase beta gene encodes multiple isoforms that display distinct kinase activity. Hsu, L.S., Chen, G.D., Lee, L.S., Chi, C.W., Cheng, J.F., Chen, J.Y. J. Biol. Chem. (2001) [Pubmed]
  23. Regulation of cyclin D1/Cdk4 complexes by calcium/calmodulin-dependent protein kinase I. Kahl, C.R., Means, A.R. J. Biol. Chem. (2004) [Pubmed]
  24. Calcium/calmodulin-dependent kinase I and calcium/calmodulin-dependent kinase kinase participate in the control of cell cycle progression in MCF-7 human breast cancer cells. Rodriguez-Mora, O.G., LaHair, M.M., McCubrey, J.A., Franklin, R.A. Cancer Res. (2005) [Pubmed]
  25. Inhibitory cross-talk by cAMP kinase on the calmodulin-dependent protein kinase cascade. Wayman, G.A., Tokumitsu, H., Soderling, T.R. J. Biol. Chem. (1997) [Pubmed]
  26. Calcium/calmodulin-dependent protein kinase II downregulates both calcineurin and protein kinase C-mediated pathways for cytokine gene transcription in human T cells. Hama, N., Paliogianni, F., Fessler, B.J., Boumpas, D.T. J. Exp. Med. (1995) [Pubmed]
  27. Molecular cloning and characterization of CLICK-III/CaMKIgamma, a novel membrane-anchored neuronal Ca2+/calmodulin-dependent protein kinase (CaMK). Takemoto-Kimura, S., Terai, H., Takamoto, M., Ohmae, S., Kikumura, S., Segi, E., Arakawa, Y., Furuyashiki, T., Narumiya, S., Bito, H. J. Biol. Chem. (2003) [Pubmed]
  28. Novel (Rp)-cAMPS analogs as tools for inhibition of cAMP-kinase in cell culture. Basal cAMP-kinase activity modulates interleukin-1 beta action. Gjertsen, B.T., Mellgren, G., Otten, A., Maronde, E., Genieser, H.G., Jastorff, B., Vintermyr, O.K., McKnight, G.S., Døskeland, S.O. J. Biol. Chem. (1995) [Pubmed]
  29. Spectroscopic characterization of the interaction between calmodulin-dependent protein kinase I and calmodulin. Gomes, A.V., Barnes, J.A., Vogel, H.J. Arch. Biochem. Biophys. (2000) [Pubmed]
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