Document Detail


Regulation of large conductance calcium- and voltage-activated potassium (BK) channels by S-palmitoylation.
MedLine Citation:
PMID:  23356260     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BK (large conductance calcium- and voltage-activated potassium) channels are important determinants of physiological control in the nervous, endocrine and vascular systems with channel dysfunction associated with major disorders ranging from epilepsy to hypertension and obesity. Thus the mechanisms that control channel surface expression and/or activity are important determinants of their (patho)physiological function. BK channels are S-acylated (palmitoylated) at two distinct sites within the N- and C-terminus of the pore-forming α-subunit. Palmitoylation of the N-terminus controls channel trafficking and surface expression whereas palmitoylation of the C-terminal domain determines regulation of channel activity by AGC-family protein kinases. Recent studies are beginning to reveal mechanistic insights into how palmitoylation controls channel trafficking and cross-talk with phosphorylation-dependent signalling pathways. Intriguingly, each site of palmitoylation is regulated by distinct zDHHCs (palmitoyl acyltransferases) and APTs (acyl thioesterases). This supports that different mechanisms may control substrate specificity by zDHHCs and APTs even within the same target protein. As palmitoylation is dynamically regulated, this fundamental post-translational modification represents an important determinant of BK channel physiology in health and disease.
Authors:
Michael J Shipston
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biochemical Society transactions     Volume:  41     ISSN:  1470-8752     ISO Abbreviation:  Biochem. Soc. Trans.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-29     Completed Date:  2013-08-02     Revised Date:  2014-04-17    
Medline Journal Info:
Nlm Unique ID:  7506897     Medline TA:  Biochem Soc Trans     Country:  England    
Other Details:
Languages:  eng     Pagination:  67-71     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Large-Conductance Calcium-Activated Potassium Channels / chemistry,  metabolism*
Lipoylation*
Palmitic Acid / metabolism*
Phosphorylation
Protein Kinases / metabolism
Signal Transduction
Grant Support
ID/Acronym/Agency:
082407//Wellcome Trust
Chemical
Reg. No./Substance:
0/Large-Conductance Calcium-Activated Potassium Channels; 2V16EO95H1/Palmitic Acid; EC 2.7.-/Protein Kinases

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