Mechanism of regulation of the gap junction protein connexin 43 by protein kinase C-mediated phosphorylation

Xiaoyong Bao, Guillermo A. Altenberg, Luis Reuss

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

Phosphorylation of the gap junction protein connexin 43 (Cx43) by protein kinase C (PKC) decreases dye coupling in many cell types. We report an investigation of the regulation by PKC of Cx43 gap junctional hemichannels (GJH) expressed in Xenopus laevis oocytes. The activity of GJH was assessed from the uptake of hydrophilic fluorescent probes. PKC inhibitors increased probe uptake in isolated oocytes expressing recombinant Cx43, indicating that the regulatory effect occurs at the hemichannel level. We identified by mutational analysis the carboxy-terminal (CT) domain sequences involved in this response. We found that 1) Ser368 is responsible for the regulation of Cx43 GJH solute permeability by PKC-mediated phosphorylation, 2) CT domain residues 253-270 and 288-359 are not necessary for the effect of PKC, and 3) the proline-rich CT region is not involved in the effect of phosphorylation by PKC. Our results demonstrate that Ser368 (but not Ser372) is involved in the regulation of Cx43 solute permeability by PKC-mediated phosphorylation, and we conclude that different molecular mechanisms underlie the regulation of Cx43 by intracellular pH and PKC-mediated phosphorylation.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume286
Issue number3 55-3
StatePublished - Mar 2004

Fingerprint

Connexin 43
Phosphorylation
Connexins
Protein Kinase C
Oocytes
Permeability
Protein C Inhibitor
Xenopus laevis
Protein Kinase Inhibitors
Fluorescent Dyes
Proline
Coloring Agents

Keywords

  • Dye loading
  • Hemichannel
  • Protein kinase C blocker

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Mechanism of regulation of the gap junction protein connexin 43 by protein kinase C-mediated phosphorylation. / Bao, Xiaoyong; Altenberg, Guillermo A.; Reuss, Luis.

In: American Journal of Physiology - Cell Physiology, Vol. 286, No. 3 55-3, 03.2004.

Research output: Contribution to journalArticle

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