Document Type

Article

Version Deposited

Published Version

Publication Date

6-29-2007

Publication Title

Journal of Biological Chemistry

DOI

10.1074/jbc.M608980200

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.

Comments

Available on publisher's website: http://www.jbc.org/content/282/26/18914.long

Authors of manuscripts, submitted at any time, need not contact the journal to request permission to reuse their own material. Authors who granted ASBMB exclusive license to publish and authors who transferred copyright to ASBMB, are allowed to do the following:

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Published Citation

Shen Y, Khusial PR, Li X, Ichikawa H, Moreno AP, Goldberg GS. SRC utilizes Cas to block gap junctional communication mediated by connexin43. J Biol Chem. 2007 Jun 29;282(26):18914-21. Epub 2007 May 7. doi: 10.1074/jbc.M608980200. PMID: 17488714.

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