Src utilizes cas to block gap junctional communication mediated by connexin43

Yongquan Shen, R. Raaj Khusial, Xun Li, Hitoshi Ichikawa, Alonso P. Moreno, Gary S. Goldberg

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

The Src tyrosine kinase phosphorylates Cas (Crk-associated substrate) to confer anchorage independence and invasive growth potential to transformed cells. Gap junctional communication is often lower between aggressive tumor cells compared with normal or benign precursors. The gap junction protein connexin43 (Cx43) is a tumor suppressor that can inhibit tumor cell growth. Src can phosphorylate Cx43 to block gap junctional communication between transformed cells. However, mechanisms by which this event actually closes intercellular channels have not been clearly defined. Here, we report that Src and Cas associate with each other at intercellular junctions. In addition, Cas is required for Src to reduce dye transfer and electrical coupling between cells expressing Cx43. Thus, Src utilizes Cas to inhibit gap junctional communication mediated by Cx43. This finding introduces a novel role of the Cas focal adhesion linker protein in the gap junction complex. This observation may help explain how gap junctional communication can be suppressed between malignant and metastatic tumor cells.

Original languageEnglish (US)
Pages (from-to)18914-18921
Number of pages8
JournalJournal of Biological Chemistry
Volume282
Issue number26
DOIs
StatePublished - Jun 29 2007

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Src utilizes cas to block gap junctional communication mediated by connexin43'. Together they form a unique fingerprint.

Cite this