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Gene Review

CAMK1  -  calcium/calmodulin-dependent protein kinase I

Homo sapiens

Synonyms: CaM kinase I, CaM kinase I alpha, CaM-KI, CaMKI, CaMKI-alpha, ...
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Disease relevance of CAMK1


High impact information on CAMK1

  • Multifunctional CaM kinase also attenuated interleukin-2 activation by calcineurin plus phorbol ester [3].
  • T-cell receptor signalling activates multifunctional CaM kinase [3].
  • 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 [4].
  • CaMKK and CaMKIV localize both to the nucleus and to the cytoplasm, whereas CaMKI is only cytosolic [5].
  • Replacement of Thr177 with Ala or Asp prevented both phosphorylation and activation by CaMKI kinase and the latter replacement also led to partial activation in the absence of CaMKI kinase [6].

Biological context of CAMK1

  • Therefore, we hypothesize that KN-93 prevents a very late, uncharacterized step in cyclin D/cdk4 activation that involves CaMKI and follows complex assembly, nuclear entry, and phosphorylation [7].
  • Mutational analysis of the 5'-flanking region of CYP11B2 revealed that a cAMP regulatory element (-71/-64) was necessary for CaMKI induction of reporter gene activity [8].
  • The 1.5 kb CaMKI mRNA is expressed in many different human tissues and is the product of a single gene located on human chromosome 3 [6].
  • The kinetics of bacterially expressed human CaMKI show that the peptide syntide-2 is a relatively poor substrate, whereas the synapsin site-1 peptide is 17-fold more specific [9].
  • The similarity of this motif to that of CaMKI [Lee, J. C., Kwon, Y.-G., Lawrence, D. S., and Edelman, A. M. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 6413-6417] is consistent with the 59% level of amino acid sequence similarity between their catalytic domains [10].

Anatomical context of CAMK1

  • CaMKI expression was shown in adrenal cortex and H295R cells using immunohistochemistry and Western and Northern analyses [8].
  • CaMKI is a Ca2+/calmodulin-dependent protein kinase that is widely expressed in eukaryotic cells and tissues but for which few, if any, physiological substrates are known [11].
  • CaM-KI inhibition with either KN-93 or specific interfering RNA (siRNA) caused an arrest in the cell cycle in the human breast cancer cell line, MCF-7 [1].
  • While screening for protein kinases expressed in the murine mammary gland, we identified previously a Ca2+/calmodulin-dependent kinase, Pnck, that is most closely related to CaMKI [12].
  • In intact PC12 cells, activation of PKA with forskolin resulted in a rapid inhibition of both CaMKK and CaMKI activity [13].

Associations of CAMK1 with chemical compounds

  • CaMKI augmented reporter expression when cellular calcium was elevated by ionomycin, whereas CaMKIV had a small effect, and CaMKII had no effect [8].
  • These findings suggest that CaMKI is involved in angiotensin II and K(+) stimulation of CYP11B2 transcription and, therefore, the capacity of the adrenal to produce aldosterone [8].
  • These data indicate a role for CaM kinase stimulation and resultant threonine phosphorylation of NMHC-IIA in RBL-2H3 m1 cell activation [14].
  • Thus, our results indicate that Ca(2+) triggers cross-talk signal transduction between CaM kinase and NO and CaM-K IIalpha phosphorylating nNOS on Ser(847), which in turn decreases the gaseous second messenger NO in neuronal cells [15].
  • In contrast, CaMKI transcript and protein is expressed in uninduced cells and is induced by all-trans retinoic acid [16].

Physical interactions of CAMK1

  • The CaMKI complex demonstrates a collapse analogous to that observed for MLCK, PDE, and SIV, while the SIV-N shows only a partial collapse [17].

Enzymatic interactions of CAMK1

  • Endogenous eIF4GII immunoprecipitated from HEK293T cells was phosphorylated by CaMKI, in vitro as was a recombinant fragment of eIF4GII encompassing the central and C-terminal regions [11].

Other interactions of CAMK1


Analytical, diagnostic and therapeutic context of CAMK1


  1. 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]
  2. 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]
  3. Interleukin-2 transcriptional block by multifunctional Ca2+/calmodulin kinase. Nghiem, P., Ollick, T., Gardner, P., Schulman, H. Nature (1994) [Pubmed]
  4. The multifunctional Ca2+/calmodulin-dependent protein kinases. Schulman, H. Curr. Opin. Cell Biol. (1993) [Pubmed]
  5. The Ca-calmodulin-dependent protein kinase cascade. Soderling, T.R. Trends Biochem. Sci. (1999) [Pubmed]
  6. Human calcium-calmodulin dependent protein kinase I: cDNA cloning, domain structure and activation by phosphorylation at threonine-177 by calcium-calmodulin dependent protein kinase I kinase. Haribabu, B., Hook, S.S., Selbert, M.A., Goldstein, E.G., Tomhave, E.D., Edelman, A.M., Snyderman, R., Means, A.R. EMBO J. (1995) [Pubmed]
  7. Regulation of cyclin D1/Cdk4 complexes by calcium/calmodulin-dependent protein kinase I. Kahl, C.R., Means, A.R. J. Biol. Chem. (2004) [Pubmed]
  8. 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]
  9. Characterization of substrate phosphorylation and use of calmodulin mutants to address implications from the enzyme crystal structure of calmodulin-dependent protein kinase I. Chin, D., Winkler, K.E., Means, A.R. J. Biol. Chem. (1997) [Pubmed]
  10. Catalytic and regulatory domains of doublecortin kinase-1. Shang, L., Kwon, Y.G., Nandy, S., Lawrence, D.S., Edelman, A.M. Biochemistry (2003) [Pubmed]
  11. Phosphorylation screening identifies translational initiation factor 4GII as an intracellular target of Ca(2+)/calmodulin-dependent protein kinase I. Qin, H., Raught, B., Sonenberg, N., Goldstein, E.G., Edelman, A.M. J. Biol. Chem. (2003) [Pubmed]
  12. 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]
  13. Inhibition of the Ca2+/calmodulin-dependent protein kinase I cascade by cAMP-dependent protein kinase. Matsushita, M., Nairn, A.C. J. Biol. Chem. (1999) [Pubmed]
  14. Calcium-dependent threonine phosphorylation of nonmuscle myosin in stimulated RBL-2H3 mast cells. Buxton, D.B., Adelstein, R.S. J. Biol. Chem. (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. Modulation of a calcium/calmodulin-dependent protein kinase cascade by retinoic acid during neutrophil maturation. Lawson, N.D., Zain, M., Zibello, T., Picciotto, M.R., Nairn, A.C., Berliner, N. Exp. Hematol. (1999) [Pubmed]
  17. Protein conformational changes studied by diffusion NMR spectroscopy: application to helix-loop-helix calcium binding proteins. Weljie, A.M., Yamniuk, A.P., Yoshino, H., Izumi, Y., Vogel, H.J. Protein Sci. (2003) [Pubmed]
  18. Comparison of gene expression profiles of lymphoma cell lines from transformed follicular lymphoma, Burkitt's lymphoma and de novo diffuse large B-cell lymphoma. Maesako, Y., Uchiyama, T., Ohno, H. Cancer Sci. (2003) [Pubmed]
  19. 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]
  20. Spatiotemporal expression of four isoforms of Ca(2+)/calmodulin-dependent protein kinase I in brain and its possible roles in hippocampal dendritic growth. Kamata, A., Sakagami, H., Tokumitsu, H., Owada, Y., Fukunaga, K., Kondo, H. Neurosci. Res. (2007) [Pubmed]
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