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SRC utilizes Cas to block gap junctional communication mediated by connexin43

Yongquan Shen1, P Raaj Khusial, Xun Li

  • 1Department of Molecular Biology, Science Center, University of Medicine and Dentistry, Stratford, New Jersey 08084, USA.

The Journal of Biological Chemistry
|May 10, 2007
PubMed

Insights

Src tyrosine kinase uses Cas to inhibit gap junction communication mediated by connexin43 (Cx43), a novel mechanism potentially explaining suppressed communication in aggressive tumors.

Area of Science:

  • Cell Biology
  • Molecular Oncology
  • Biochemistry

Background:

  • Gap junctional communication is reduced in aggressive tumor cells.
  • Connexin43 (Cx43) is a tumor suppressor that inhibits cell growth.
  • Src tyrosine kinase phosphorylates Cx43, potentially blocking gap junction communication.

Purpose of the Study:

  • To elucidate the mechanism by which Src inhibits Cx43-mediated gap junctional communication.
  • To investigate the role of Crk-associated substrate (Cas) in this process.

Main Methods:

  • Co-immunoprecipitation to detect protein-protein interactions.
  • Dye transfer assays to measure gap junctional communication.
  • Electrical coupling measurements.

Main Results:

  • Src and Cas associate at intercellular junctions.
  • Cas is essential for Src to reduce dye transfer and electrical coupling in Cx43-expressing cells.
  • Src utilizes Cas to inhibit Cx43-mediated gap junctional communication.

Conclusions:

  • Src inhibits gap junctional communication via Cx43 by utilizing the Cas protein.
  • Cas plays a novel role in the gap junction complex.
  • This mechanism may explain suppressed gap junctional communication in malignant and metastatic tumor cells.

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