Document Detail

Phosphorylation of connexin 50 by protein kinase A enhances gap junction and hemichannel function.
MedLine Citation:
PMID:  21454606     Owner:  NLM     Status:  MEDLINE    
Phosphorylation of connexins is an important mechanism regulating gap junction channels. However, the role(s) of connexin (Cx) phosphorylation in vivo are largely unknown. Here, we showed by mass spectrometry that Ser-395 in the C terminus of chicken Cx50 was phosphorylated in the lens. Ser-395 is located within a PKA consensus site. Analyses of Cx50 phosphorylation by two-dimensional thin layer chromatography tryptic phosphopeptide profiles suggested that Ser-395 was targeted by PKA in vivo. PKA activation increased both gap junction dye coupling and hemichannel dye uptake in a manner not involving increases in total Cx50 expression or relocation to the cell surface or gap junctional plaques. Single channel recordings indicated PKA enhanced transitions between the closed and ∼200-pS open state while simultaneously reducing transitions between this open state and a ∼65-pS subconductance state. The mutation of Ser-395 to alanine significantly attenuated PKA-induced increases in dye coupling and uptake by Cx50. However, channel records indicated that phosphorylation at this site was unnecessary for enhanced transitions between the closed and ∼200-pS conductance state. Together, these results suggest that Cx50 is phosphorylated in vivo by PKA at Ser-395 and that this event, although unnecessary for PKA-induced alterations in channel conductance, promotes increased dye permeability of Cx50 channels, which plays an important role in metabolic coupling and transport in lens fibers.
Jialu Liu; Jose F Ek Vitorin; Susan T Weintraub; Sumin Gu; Qian Shi; Janis M Burt; Jean X Jiang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-03-24
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  286     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-05-09     Completed Date:  2011-07-12     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  16914-28     Citation Subset:  IM    
Department of Biochemistry, University of Texas Health Science Center, San Antonio, Texas 78229, USA.
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MeSH Terms
Cell Membrane / metabolism
Chick Embryo
Chromatography, High Pressure Liquid / methods
Chromatography, Thin Layer / methods
Connexins / chemistry*
Cyclic AMP-Dependent Protein Kinases / chemistry,  metabolism*
Eye Proteins / chemistry*
Gap Junctions / metabolism*
Mass Spectrometry / methods
Phosphopeptides / chemistry
Recombinant Proteins / chemistry
Serine / chemistry
Spectrometry, Mass, Electrospray Ionization / methods
Trypsin / chemistry
Grant Support
Reg. No./Substance:
0/Connexins; 0/Eye Proteins; 0/Phosphopeptides; 0/Recombinant Proteins; 0/connexin 50; 56-45-1/Serine; EC AMP-Dependent Protein Kinases; EC

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