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Article
Mutation of protein kinase C phosphorylation site S1076 on α-subunits affects BKCa channel activity in HEK-293 cells
American Journal of Physiology - Lung Cellular and Molecular Physiology
  • Shu Zhu, Philadelphia College of Osteopathic Medicine
  • Darren D. Browning
  • Richard E. White
  • David Fulton
  • Scott A. Barman
Document Type
Article
Publication Date
1-1-2009
Abstract
Large conductance, calcium- and voltage-activated potassium (BK Ca) channels are important modulators of pulmonary vascular smooth muscle membrane potential, and phosphorylation of BKCa channels by protein kinases regulates pulmonary arterial smooth muscle function. However, little is known about the effect of phosphorylating specific channel subunits on BKCa channel activity. The present study was done to determine the effect of mutating protein kinase C (PKC) phosphorylation site serine 1076 (S1076) on transfected human BKCa channel α-subunits in human embryonic kidney (HEK-293) cells, a heterologous expression system devoid of endogenous BKCa channels. Results showed that mutating S1076 altered the effect of PKC activation on BKCa channels in HEK-293 cells. Specifically, the phospho-deficient mutation BKCa-α(S1076A)/ β1 attenuated the excitatory effect of the PKC activator phorbol myristate acetate (PMA) on BKCa channels, whereas the phospho-mimetic mutation BKCa-α(S1076E)/β1 increased the excitatory effect of PMA on BKCa channels. In addition, the phosphonull mutation S1076A blocked the activating effect of cGMP-dependent protein kinase G (PKG) on BKCa channels. Collectively, these results suggest that specific putative PKC phosphorylation site(s) on human BK Ca channel α-subunits influences BKCa channel activity, which may subsequently alter pulmonary vascular smooth muscle function and tone.
Comments

This article was published in American Journal of Physiology - Lung Cellular and Molecular Physiology, Volume 297, Issue 4, Pages L758-L766.

The published version is available at http://dx.doi.org/10.1152/ajplung.90518.2008.

Copyright © 2009 Scopus.

Citation Information
Shu Zhu, Darren D. Browning, Richard E. White, David Fulton, et al.. "Mutation of protein kinase C phosphorylation site S1076 on α-subunits affects BKCa channel activity in HEK-293 cells" American Journal of Physiology - Lung Cellular and Molecular Physiology Vol. 297 Iss. 4 (2009) p. L758 - L766
Available at: http://works.bepress.com/richard_white/22/