Alternative Splicing Switches Potassium Channel Sensitivity to Protein Phosphorylation

Lijun Tian, Rory R. Duncan, Martin S L Hammond, Lorraine S. Coghill, Hua Wen, Radda Rusinova, Alan G. Clark, Irwin B. Levitan, Michael J. Shipston

Research output: Contribution to journalArticle

170 Citations (Scopus)

Abstract

Alternative exon splicing and reversible protein phosphorylation of large conductance calcium-activated potassium (BK) channels represent fundamental control mechanisms for the regulation of cellular excitability. BK channels are encoded by a single gene that undergoes extensive, hormonally regulated exon splicing. In native tissues BK channels display considerable diversity and plasticity in their regulation by cAMP-dependent protein kinase (PKA). Differential regulation of alternatively spliced BK channels by PKA may provide a molecular basis for the diversity and plasticity of BK channel sensitivities to PKA. Here we demonstrate that PKA activates BK channels lacking splice inserts (ZERO) but inhibits channels expressing a 59-amino acid exon at splice site 2 (STREX-1). Channel activation is dependent upon a conserved C-terminal PKA consensus motif (S869), whereas inhibition is mediated via a STREX-1 exon-specific PKA consensus site. Thus, alternative splicing acts as a molecular switch to determine the sensitivity of potassium channels to protein phosphorylation.

Original languageEnglish (US)
Pages (from-to)7717-7720
Number of pages4
JournalJournal of Biological Chemistry
Volume276
Issue number11
DOIs
StatePublished - Mar 16 2001
Externally publishedYes

Fingerprint

Large-Conductance Calcium-Activated Potassium Channels
Phosphorylation
Potassium Channels
Alternative Splicing
Protein Kinases
Switches
Exons
Proteins
Plasticity
Cyclic AMP-Dependent Protein Kinases
Potassium
Protein Kinase C
Genes
Chemical activation
Tissue
Calcium
Amino Acids

ASJC Scopus subject areas

  • Biochemistry

Cite this

Tian, L., Duncan, R. R., Hammond, M. S. L., Coghill, L. S., Wen, H., Rusinova, R., ... Shipston, M. J. (2001). Alternative Splicing Switches Potassium Channel Sensitivity to Protein Phosphorylation. Journal of Biological Chemistry, 276(11), 7717-7720. https://doi.org/10.1074/jbc.C000741200

Alternative Splicing Switches Potassium Channel Sensitivity to Protein Phosphorylation. / Tian, Lijun; Duncan, Rory R.; Hammond, Martin S L; Coghill, Lorraine S.; Wen, Hua; Rusinova, Radda; Clark, Alan G.; Levitan, Irwin B.; Shipston, Michael J.

In: Journal of Biological Chemistry, Vol. 276, No. 11, 16.03.2001, p. 7717-7720.

Research output: Contribution to journalArticle

Tian, L, Duncan, RR, Hammond, MSL, Coghill, LS, Wen, H, Rusinova, R, Clark, AG, Levitan, IB & Shipston, MJ 2001, 'Alternative Splicing Switches Potassium Channel Sensitivity to Protein Phosphorylation', Journal of Biological Chemistry, vol. 276, no. 11, pp. 7717-7720. https://doi.org/10.1074/jbc.C000741200
Tian, Lijun ; Duncan, Rory R. ; Hammond, Martin S L ; Coghill, Lorraine S. ; Wen, Hua ; Rusinova, Radda ; Clark, Alan G. ; Levitan, Irwin B. ; Shipston, Michael J. / Alternative Splicing Switches Potassium Channel Sensitivity to Protein Phosphorylation. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 11. pp. 7717-7720.
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