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KCNMB4  -  potassium channel subfamily M regulatory...

Homo sapiens

Synonyms: BK channel subunit beta-4, BKbeta4, Calcium-activated potassium channel subunit beta-4, Calcium-activated potassium channel, subfamily M subunit beta-4, Charybdotoxin receptor subunit beta-4, ...
 
 
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Disease relevance of KCNMB4

  • Taxol-resistant lung cancer cells, A549-T24, which are 17-fold resistant to Taxol and display a fourfold increase in Hbeta4 expression compared to the parental A549 cells, were treated with 1 microM antisense ODNs [1].
 

High impact information on KCNMB4

  • Phosphorylation-dependent functional coupling of hSlo calcium-dependent potassium channel and its hbeta 4 subunit [2].
  • Cloning and functional characterization of novel large conductance calcium-activated potassium channel beta subunits, hKCNMB3 and hKCNMB4 [3].
  • In contrast, hKCNMB4 slows Hslo1 gating kinetics, and modulates the apparent calcium sensitivity of Hslo1 [3].
  • We present the cloning and characterization of two novel calcium-activated potassium channel beta subunits, hKCNMB3 and hKCNMB4, that are enriched in the testis and brain, respectively [3].
  • HM40 was the predominant, accounting for 84.7-98.7% of all tubulin; expression of the other four isotypes (Hbeta9, Hbeta4, H5beta, and Hbeta2) was also detected but at lower levels [4].
 

Biological context of KCNMB4

  • BKbeta4 slowed activation kinetics more significantly, led to a steeper apparent calcium sensitivity, and shifted the voltage range of BK current activation to more negative potentials than BKbeta1 [5].
 

Anatomical context of KCNMB4

  • Profiling mRNA expression showed that hKCNMB3 expression is enriched in testis and hKCNMB4 expression is very prominent in brain [5].
  • We coexpressed BK channel alpha (BKalpha) and BKbeta4 subunits in vitro in CHO cells [5].
  • A similar pattern of beta-tubulin isotype expression was observed in a subset of cell lines from the National Cancer Institute-Anticancer Drug Screen. In these cell lines, however, a significant correlation between increased expression of Hbeta4 isotype and resistance to paclitaxel was found [4].
 

Associations of KCNMB4 with chemical compounds

  • (Brenner, R., Jegla, T.J., Wickenden, A., Liu, Y., Aldrich, R.W. 2000. Cloning and functional expression of novel large-conductance calcium-activated potassium channel beta subunits, hKCNMB3 and hKCNMB4. J. Biol. Chem.275:6453-6461.)[6]
  • To evaluate directly the role of the class III beta-tubulin isotype in mediating Taxol resistance, antisense phosphorothioate oligodeoxynucleotides (ODN) targeted against various regions of the Hbeta4 gene have been designed and examined for their efficacy in reducing Hbeta4 gene and protein expression [1].

References

  1. Antisense oligonucleotides to class III beta-tubulin sensitize drug-resistant cells to Taxol. Kavallaris, M., Burkhart, C.A., Horwitz, S.B. Br. J. Cancer (1999) [Pubmed]
  2. Phosphorylation-dependent functional coupling of hSlo calcium-dependent potassium channel and its hbeta 4 subunit. Jin, P., Weiger, T.M., Wu, Y., Levitan, I.B. J. Biol. Chem. (2002) [Pubmed]
  3. Cloning and functional characterization of novel large conductance calcium-activated potassium channel beta subunits, hKCNMB3 and hKCNMB4. Brenner, R., Jegla, T.J., Wickenden, A., Liu, Y., Aldrich, R.W. J. Biol. Chem. (2000) [Pubmed]
  4. Expression of beta-tubulin isotypes in human ovarian carcinoma xenografts and in a sub-panel of human cancer cell lines from the NCI-Anticancer Drug Screen: correlation with sensitivity to microtubule active agents. Nicoletti, M.I., Valoti, G., Giannakakou, P., Zhan, Z., Kim, J.H., Lucchini, V., Landoni, F., Mayo, J.G., Giavazzi, R., Fojo, T. Clin. Cancer Res. (2001) [Pubmed]
  5. hKCNMB3 and hKCNMB4, cloning and characterization of two members of the large-conductance calcium-activated potassium channel beta subunit family. Behrens, R., Nolting, A., Reimann, F., Schwarz, M., Waldschütz, R., Pongs, O. FEBS Lett. (2000) [Pubmed]
  6. Properties of BK(Ca) channels formed by bicistronic expression of hSloalpha and beta1-4 subunits in HEK293 cells. Lippiat, J.D., Standen, N.B., Harrow, I.D., Phillips, S.C., Davies, N.W. J. Membr. Biol. (2003) [Pubmed]
 
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