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Gene Review

CAMK4  -  calcium/calmodulin-dependent protein...

Homo sapiens

Synonyms: CAMK, CAMK-GR, CAMKIV, CaM kinase-GR, CaMK IV, ...
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Disease relevance of CAMK4


High impact information on CAMK4

  • It is initiated by a highly local, rise in calcium ion concentrations near the cell membrane, but culminates in the activation of a specific calmodulin-dependent kinase known as CaMK IV, which is constitutively present in the neuronal nucleus [4].
  • Multifunctional Ca2+/calmodulin-dependent (CaM) kinase, CaM kinase Ia, CaM kinase Ib and CaM kinase IV are four of the kinases that mediate Ca(2+)-signaling pathways [5].
  • These results show that Op18 phosphorylation by CaMK IV/Gr may couple alterations of MT dynamics in response to external signals that involve Ca2+ [6].
  • In addition to cell cycle-regulated phosphorylation, external signals induce phosphorylation of Op18 on Ser-25 by the mitogen-activated protein kinase and on Ser-16 by the Ca2+/calmodulin-dependent kinase IV/Gr (CaMK IV/Gr) [6].
  • They also exhibit a distinct ability to undergo autophosphorylation and to phosphorylate the downstream kinases CaMK I and CaMK IV [7].

Biological context of CAMK4


Anatomical context of CAMK4


Associations of CAMK4 with chemical compounds

  • Calmodulin-dependent protein kinase IV (CaM-kinase IV) phosphorylated calmodulin (CaM), which is its own activator, in a poly-L-Lys [poly(Lys)]-dependent manner [14].
  • The optimum concentration of poly(Lys) for the phosphorylation of 1 microM CaM was about 10 microg/ml, but poly(Lys) strongly inhibited CaM-kinase IV activity toward syntide-2 at this concentration, suggesting that the phosphorylation of CaM is not due to simple activation of the catalytic activity [14].
  • The recombinant mutant CaM-kinase IV in which Thr196 or Thr200 was replaced with nonphosphorylatable alanine showed little activity in the presence and absence of the kinase kinase [15].
  • Synaptic activity, acting via the nuclear Ca(2+)-dependent activation of CaM kinase IV, triggers the disruption of subnuclear domains containing class II histone deacetylases (HDACs) and silencing mediator of retinoic acid and thyroid hormone receptors (SMRT), a broad-specificity co-repressor which represses nuclear hormone receptors and CBF1 [16].
  • The CaM kinase-Gr is only expressed in certain lymphoid cell lines, and the present study shows that ionomycin-induced phosphorylation of Op18 Ser16 is restricted to cells expressing this protein kinase [17].

Enzymatic interactions of CAMK4

  • CaM-K Ialpha and CaM-K IV failed to phosphorylate nNOS at Ser(847) in transfected cells [18].

Regulatory relationships of CAMK4


Other interactions of CAMK4


Analytical, diagnostic and therapeutic context of CAMK4


  1. A Ca2+/calmodulin-dependent protein kinase, CaM kinase-Gr, expressed after transformation of primary human B lymphocytes by Epstein-Barr virus (EBV) is induced by the EBV oncogene LMP1. Mosialos, G., Hanissian, S.H., Jawahar, S., Vara, L., Kieff, E., Chatila, T.A. J. Virol. (1994) [Pubmed]
  2. cDNA cloning and expression of human calmodulin-dependent protein kinase IV. Kitani, T., Okuno, S., Fujisawa, H. J. Biochem. (1994) [Pubmed]
  3. Effects of magnesium sulfate administration during hypoxia on CaM Kinase IV and Protein Tyrosine Kinase Activities in the cerebral cortex of newborn piglets. Mami, A.G., Ballesteros, J.R., Fritz, K.I., Kubin, J., Mishra, O.P., Delivoria-Papadopoulos, M. Neurochem. Res. (2006) [Pubmed]
  4. Translocation of calmodulin to the nucleus supports CREB phosphorylation in hippocampal neurons. Deisseroth, K., Heist, E.K., Tsien, R.W. Nature (1998) [Pubmed]
  5. The multifunctional Ca2+/calmodulin-dependent protein kinases. Schulman, H. Curr. Opin. Cell Biol. (1993) [Pubmed]
  6. Regulation of microtubule dynamics by Ca2+/calmodulin-dependent kinase IV/Gr-dependent phosphorylation of oncoprotein 18. Melander Gradin, H., Marklund, U., Larsson, N., Chatila, T.A., Gullberg, M. Mol. Cell. Biol. (1997) [Pubmed]
  7. 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]
  8. Molecular mechanism of neuronal plasticity: induction and maintenance of long-term potentiation in the hippocampus. Miyamoto, E. J. Pharmacol. Sci. (2006) [Pubmed]
  9. Phosphorylation of CREB by CaM-kinase IV activated by CaM-kinase IV kinase. Enslen, H., Tokumitsu, H., Soderling, T.R. Biochem. Biophys. Res. Commun. (1995) [Pubmed]
  10. Interactions of calcium/calmodulin-dependent protein kinases (CaMK) and extracellular-regulated kinase (ERK) in monocyte adherence and TNFalpha production. Rosengart, M.R., Arbabi, S., Garcia, I., Maier, R.V. Shock (2000) [Pubmed]
  11. The cDNA sequence and characterization of the Ca2+/calmodulin-dependent protein kinase-Gr from human brain and thymus. Bland, M.M., Monroe, R.S., Ohmstede, C.A. Gene (1994) [Pubmed]
  12. Expression of a Ca2+/calmodulin-dependent protein kinase, CaM kinase-Gr, in human T lymphocytes. Regulation of kinase activity by T cell receptor signaling. Hanissian, S.H., Frangakis, M., Bland, M.M., Jawahar, S., Chatila, T.A. J. Biol. Chem. (1993) [Pubmed]
  13. Exercise and CaMK activation both increase the binding of MEF2A to the Glut4 promoter in skeletal muscle in vivo. Smith, J.A., Collins, M., Grobler, L.A., Magee, C.J., Ojuka, E.O. Am. J. Physiol. Endocrinol. Metab. (2007) [Pubmed]
  14. Phosphorylation of calmodulin by Ca2+/calmodulin-dependent protein kinase IV. Ishida, A., Kameshita, I., Okuno, S., Kitani, T., Fujisawa, H. Arch. Biochem. Biophys. (2002) [Pubmed]
  15. Studies on the site of phosphorylation of Ca2+/calmodulin-dependent protein kinase (CaM-kinase) IV by CaM-kinase kinase. Kitani, T., Okuno, S., Fujisawa, H. J. Biochem. (1997) [Pubmed]
  16. Nuclear Ca2+ and CaM kinase IV specify hormonal- and Notch-responsiveness. McKenzie, G.J., Stevenson, P., Ward, G., Papadia, S., Bading, H., Chawla, S., Privalsky, M., Hardingham, G.E. J. Neurochem. (2005) [Pubmed]
  17. Serine 16 of oncoprotein 18 is a major cytosolic target for the Ca2+/calmodulin-dependent kinase-Gr. Marklund, U., Larsson, N., Brattsand, G., Osterman, O., Chatila, T.A., Gullberg, M. Eur. J. Biochem. (1994) [Pubmed]
  18. Post-synaptic density-95 promotes calcium/calmodulin-dependent protein kinase II-mediated Ser847 phosphorylation of neuronal nitric oxide synthase. Watanabe, Y., Song, T., Sugimoto, K., Horii, M., Araki, N., Tokumitsu, H., Tezuka, T., Yamamoto, T., Tokuda, M. Biochem. J. (2003) [Pubmed]
  19. Enhanced expression and activation of Ca(2+)/calmodulin-dependent protein kinase IV in hepatocellular carcinoma. Tamura, N., Tai, Y., Sugimoto, K., Kobayashi, R., Konishi, R., Nishioka, M., Masaki, T., Nagahata, S., Tokuda, M. Cancer (2000) [Pubmed]
  20. Calcium/calmodulin-dependent kinase II is required for platelet-activating factor priming. Cuschieri, J., Bulger, E., Garcia, I., Jelacic, S., Maier, R.V. Shock (2005) [Pubmed]
  21. Regulation of neuronal nitric-oxide synthase by calmodulin kinases. Hayashi, Y., Nishio, M., Naito, Y., Yokokura, H., Nimura, Y., Hidaka, H., Watanabe, Y. J. Biol. Chem. (1999) [Pubmed]
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