Transduction of cell survival signals by connexin-43 hemichannels

Lilian I. Plotkin, Stavros C. Manolagas, Teresita Bellido

Research output: Contribution to journalArticle

282 Scopus citations


Bisphosphonates, drugs used widely in the treatment of bone diseases, prevent osteoblast and osteocyte apoptosis by a mechanism involving extracellular signal-regulated kinase (ERK) activation. We report herein that hexameric connexin (Cx)-43 hemichannels, but not gap junctions, are the essential transducers of the ERK- activating/anti-apoptotic effects of bisphosphonates. Transfection of Cx-43, but not other Cxs, into Cx-43 naive cells confers de novo responsiveness to the drugs. The signal-transducing property of Cx-43 requires the pore forming as well as the C-terminal domains of the protein, the activation of both Src and ERK kinases, and the SH2 and SH3 domains of Src. This evidence adds Cx-43 to the list of transmembrane proteins capable of transducing survival signals in response to extracellular cues and raises the possibility that it may serve in this capacity for endogenously produced molecules or even other drugs.

Original languageEnglish (US)
Pages (from-to)8648-8657
Number of pages10
JournalJournal of Biological Chemistry
Issue number10
StatePublished - Mar 8 2002
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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