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Gene Review

CKB  -  creatine kinase, brain

Homo sapiens

Synonyms: B-CK, BCK, CKBB, Creatine kinase B chain, Creatine kinase B-type, ...
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Disease relevance of CKB

  • These results suggest an involvement of hnRNP F and CKB in colorectal cancer [1].
  • METHODS: The 2 patients and other 26 patients with hematologic malignancies, and some cancer cell lines were subjected to measurement of serum CK activity, CK isoenzyme analysis, CKB mRNA expression analysis by RT-PCR, and methylation analysis of the CKB promoter region [2].
  • It is concluded that in most tumours there is a decrease in the expression of type B- and type M-CK subunits, whereas in lung carcinoid the expression of type B-CK activity increases [3].
  • In this report, we show that the level of CKB mRNA in human U87 glioblastoma cells can be increased by either prostaglandin E1 (PGE1), prostaglandin E2 (PGE2), or cholera toxin (an activator of G alpha s proteins) [4].
  • Although transient elevation of the CKB concentration in some patients with subarachnoid hemorrhage was observed after angiography or clinical worsening, the fluctuation in patients with ischemic stroke was not associated with worsening of neurologic conditions or recurrence of ischemic events [5].

Psychiatry related information on CKB

  • No relationship was found between levels of CKBB and level of dementia, or with the specific clinical diagnosis of senile dementia of the Alzheimer type, although a weakly positive relationship was found between CKBB and 3 cognitive scales [6].

High impact information on CKB

  • The human chromosomal assignments of genes of the creatine kinase (CK) family--loci for brain (CKBB), muscle (CKMM), and mitochondrial (CKMT) forms--were studied by Southern filter hybridization analysis of DNAs isolated from a human x rodent somatic cell hybrid clone panel [7].
  • Thus the earlier assignment of the gene coding for the CKBB isozyme to chromosome 14 was confirmed by molecular means, as was the provisional assignment of CKMM to the long arm of chromosome 19 [7].
  • Probes for the 3'-noncoding sequences of human CKBB and CKMM hybridized concordantly only to DNAs from somatic cell hybrids containing chromosomes 14 and 19, respectively [7].
  • SJL mice are more sensitive to this B-cell depletion and recover more slowly than putatively normal C3H.Ighb (CKB) mice [8].
  • We have recently detected high levels of CKB mRNA in HeLa cells and, in this study, have tested whether this may be due to the extremely low amounts of p53 protein present in HeLa cells [9].

Chemical compound and disease context of CKB

  • Our previous studies have shown that transcription of brain creatine kinase (CKB) mRNA in U87-MG glioblastoma cells is stimulated by a forskolin-mediated increase in cyclic AMP (cAMP) via a pathway involving protein kinase A (PKA) and the activation of Galphas proteins [10].
  • In this report we show that treatment of human U87 glioblastoma cells with forskolin and IBMX, to elevate intracellular cAMP, induces expression of CKB mRNA from the transiently transfected rat CKB gene by 14-fold and also increases expression from the endogenous human CKB gene [11].
  • Analysis of the CKB gene promoter in MCF-7 breast cancer cells confirmed that pCKB7 (containing the -568 to -523 promoter insert) was estrogen-responsive in transient transfection studies [12].
  • Our previous studies established in U87-MG glioblastoma cells that elevated cAMP increased transcription of the endogenous as well as a transiently-transfected brain creatine kinase (CKB) gene, despite the absence of a cAMP response element (CRE) in the CKB proximal promoter [13].
  • The posttraumatic creatine kinase-BB isoenzyme (CKBB) activity and lactate concentration in ventricular cerebrospinal fluid (CSF) have been studied in 29 patients with severe head injuries [14].

Biological context of CKB

  • A relation between CKB mRNA expression and methylation of the CKB promoter was suggested [2].
  • In disease, a decreased CKMIT and dramatically increased CKB may indicate a stressed intracellular energy transfer [15].
  • For example, the presence of brain-type B-CK in Bergmann glial cells and astrocytes is very likely related to the energy requirements for ion homeostasis (K(+)-resorption) in the brain, as well as for metabolite and neurotransmitter trafficking between glial cells and neurons [16].
  • Two different preinitiation complexes can assemble on the CKB promoter, one which initiated at the same downstream start-site used in normal adult rat brain and one which initiated 35 base pairs further upstream [17].
  • In this study we find an element at -550, aGGTCAgaaCACCCt, with limited similarity to the estrogen response element consensus, to be involved in conferring estrogen responsiveness on the CKB promoter [18].

Anatomical context of CKB

  • Surprisingly, subcellular levels of CKB were decreased in colon tumors, suggesting that the observed high CKB levels in nuclear matrix extracts are caused by the enhanced localization of CKB to the nuclear matrix during colon tumorigenesis [1].
  • Spermatogenesis-related change in the synthesis of the creatine kinase B-type and M-type isoforms in human spermatozoa [19].
  • CONCLUSIONS: Expression of CKB mRNA and CK-B sometimes occurred in blastic transformation of the hematopoietic system [2].
  • While muscle CK (CKM) is expressed almost exclusively in adult skeletal and cardiac muscle, brain CK (CKB) expression is more widespread and is highest in brain glial cells [9].
  • Small amounts of CKB in the normal left ventricle, as opposed to the right ventricular free wall, might be related to differences in myocardial perfusion during the cardiac cycle [15].

Associations of CKB with chemical compounds

  • Increased creatine kinase BB activity and CKB mRNA expression in patients with hematologic disorders: relation to methylation status of the CKB promoter [2].
  • The data used included the electrocardiogram (ECG) and the concentrations in serum of potassium, creatine kinase B-subunit (CKB), and lactate dehydrogenase isoenzyme 1 for 250 patients with suspected AMI [20].
  • In addition, the results indicate that both PGE1 and PGE2 use the same or related signal transduction pathways to increase CKB transcription [4].
  • In primary cortical neurons expressing CKB, the GABA reversal potential was also shifted in the depolarizing direction by DNFB [21].
  • Strain CKB was enriched and isolated from paper mill waste with acetate as the sole electron donor and chlorate as the sole electron acceptor [22].

Regulatory relationships of CKB

  • (2) Efficient coupling of MM-CK to myosin ATPase is seen in adult mammalian striated muscles but not in frog and bird heart where B-CK is expressed instead of M-CK [23].
  • These results suggest that in glial cells CKB mRNA can be regulated by extracellular signals acting through G-protein-coupled receptors [4].

Other interactions of CKB

  • In the present work, we examined whether in spermatozoa, similar to muscle, there is a change in the synthesis of B-CK and M-CK isoforms during cellular differentiation [19].
  • Activities of CS, CKB and CKMIT in right septal biopsies did not differ from those in left ventricular locations [15].
  • In order to study the molecular mechanism of this induction, 2.9 kb of the 5'-flanking region of CKB fused with the CAT reporter gene was cotransfected into ROS 17/2.8 and HeLa cells along with an expression plasmid for the human estrogen receptor [24].
  • CKB analysis revealed considerable bacterial diversity within the respective MSD [25].

Analytical, diagnostic and therapeutic context of CKB


  1. Altered expression and localization of creatine kinase B, heterogeneous nuclear ribonucleoprotein F, and high mobility group box 1 protein in the nuclear matrix associated with colon cancer. Balasubramani, M., Day, B.W., Schoen, R.E., Getzenberg, R.H. Cancer Res. (2006) [Pubmed]
  2. Increased creatine kinase BB activity and CKB mRNA expression in patients with hematologic disorders: relation to methylation status of the CKB promoter. Ishikawa, J., Taniguchi, T., Takeshita, A., Maekawa, M. Clin. Chim. Acta (2005) [Pubmed]
  3. Creatine kinase activity and isoenzymes in lung, colon and liver carcinomas. Joseph, J., Cardesa, A., Carreras, J. Br. J. Cancer (1997) [Pubmed]
  4. Prostaglandin E1, E2, and cholera toxin increase transcription of the brain creatine kinase gene in human U87 glioblastoma cells. Kuzhikandathil, E.V., Molloy, G.R. Glia (1995) [Pubmed]
  5. Serum creatine kinase B concentrations in acute cerebrovascular diseases. Pfeiffer, F.E., Homburger, H.A., Yanagihara, T. Arch. Neurol. (1984) [Pubmed]
  6. Serum creatine kinase BB isoenzyme levels in an epidemiological study of dementia and cognitive impairment. Brayne, C., Calloway, P. Acta psychiatrica Scandinavica. (1990) [Pubmed]
  7. Human creatine kinase genes on chromosomes 15 and 19, and proximity of the gene for the muscle form to the genes for apolipoprotein C2 and excision repair. Stallings, R.L., Olson, E., Strauss, A.W., Thompson, L.H., Bachinski, L.L., Siciliano, M.J. Am. J. Hum. Genet. (1988) [Pubmed]
  8. Disappearance and reappearance of B cells after in vivo treatment with monoclonal anti-I-A antibodies. Waldor, M.K., Hardy, R.R., Hayakawa, K., Steinman, L., Herzenberg, L.A., Herzenberg, L.A. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  9. Mouse p53 represses the rat brain creatine kinase gene but activates the rat muscle creatine kinase gene. Zhao, J., Schmieg, F.I., Simmons, D.T., Molloy, G.R. Mol. Cell. Biol. (1994) [Pubmed]
  10. Proximal promoter of the rat brain creatine kinase gene lacks a consensus CRE element but is essential for the cAMP-mediated increased transcription in glioblastoma cells. Kuzhikandathil, E.V., Molloy, G.R. J. Neurosci. Res. (1999) [Pubmed]
  11. Transcription of the brain creatine kinase gene in glial cells is modulated by cyclic AMP-dependent protein kinase. Kuzhikandathil, E.V., Molloy, G.R. J. Neurosci. Res. (1994) [Pubmed]
  12. Transcriptional activation of rat creatine kinase B by 17beta-estradiol in MCF-7 cells involves an estrogen responsive element and GC-rich sites. Wang, F., Samudio, I., Safe, S. J. Cell. Biochem. (2001) [Pubmed]
  13. Transcription of brain creatine kinase in U87-MG glioblastoma is modulated by factor AP2. Willis, D., Zhang, Y., Molloy, G.R. Biochim. Biophys. Acta (2005) [Pubmed]
  14. CSF brain creatine kinase levels and lactic acidosis in severe head injury. Rabow, L., DeSalles, A.F., Becker, D.P., Yang, M., Kontos, H.A., Ward, J.D., Moulton, R.J., Clifton, G., Gruemer, H.D., Muizelaar, J.P. J. Neurosurg. (1986) [Pubmed]
  15. Dynamics of creatine kinase shuttle enzymes in the human heart. Sylvén, C., Lin, L., Kallner, A., Sotonyi, P., Somogyi, E., Jansson, E. Eur. J. Clin. Invest. (1991) [Pubmed]
  16. Functional aspects of creatine kinase in brain. Hemmer, W., Wallimann, T. Dev. Neurosci. (1993) [Pubmed]
  17. Two different RNA polymerase II initiation complexes can assemble on the rat brain creatine kinase promoter. Mitchell, M.T., Benfield, P.A. J. Biol. Chem. (1990) [Pubmed]
  18. Delineation of sites mediating estrogen regulation of the rat creatine kinase B gene. Wu-Peng, X.S., Pugliese, T.E., Dickerman, H.W., Pentecost, B.T. Mol. Endocrinol. (1992) [Pubmed]
  19. Spermatogenesis-related change in the synthesis of the creatine kinase B-type and M-type isoforms in human spermatozoa. Huszar, G., Vigue, L. Mol. Reprod. Dev. (1990) [Pubmed]
  20. Use of neural networks to diagnose acute myocardial infarction. II. A clinical application. Pedersen, S.M., Jørgensen, J.S., Pedersen, J.B. Clin. Chem. (1996) [Pubmed]
  21. Brain-type creatine kinase activates neuron-specific K+-Cl- co-transporter KCC2. Inoue, K., Yamada, J., Ueno, S., Fukuda, A. J. Neurochem. (2006) [Pubmed]
  22. Reduction of (per)chlorate by a novel organism isolated from paper mill waste. Bruce, R.A., Achenbach, L.A., Coates, J.D. Environ. Microbiol. (1999) [Pubmed]
  23. Functional coupling of creatine kinases in muscles: species and tissue specificity. Ventura-Clapier, R., Kuznetsov, A., Veksler, V., Boehm, E., Anflous, K. Mol. Cell. Biochem. (1998) [Pubmed]
  24. Responsiveness of the 5'-flanking region of the brain type isozyme of creatine kinase to estrogens and antiestrogen. Spatz, M., Waisman, A., Kaye, A.M. J. Steroid Biochem. Mol. Biol. (1992) [Pubmed]
  25. Development and characterization of a simple perfused oral microcosm. McBain, A.J., Sissons, C., Ledder, R.G., Sreenivasan, P.K., De Vizio, W., Gilbert, P. J. Appl. Microbiol. (2005) [Pubmed]
  26. Improved quantification with validation of multiple mRNA species by polymerase chain reaction: application to human myocardial creatine kinase M and B. Ma, T.S., Brink, P.A., Perryman, B., Roberts, R. Cardiovasc. Res. (1994) [Pubmed]
  27. Clinical applications of microarray technology: creatine kinase B is an up-regulated gene in epithelial ovarian cancer and shows promise as a serum marker. Huddleston, H.G., Wong, K.K., Welch, W.R., Berkowitz, R.S., Mok, S.C. Gynecol. Oncol. (2005) [Pubmed]
  28. Regulation of creatine kinase isoenzymes in human placenta during early, mid-, and late gestation. Thomure, M.F., Gast, M.J., Srivastava, N., Payne, R.M. J. Soc. Gynecol. Investig. (1996) [Pubmed]
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