SRC utilizes Cas to block gap junctional communication mediated by connexin43.
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.
Shen
Yongquan
Y
Department of Molecular Biology, Science Center, University of Medicine and Dentistry, Stratford, New Jersey 08084, USA.
Khusial
P Raaj
PR
Li
Xun
X
Ichikawa
Hitoshi
H
Moreno
Alonso P
AP
Goldberg
Gary S
GS
D000818:Animals; D002450:Cell Communication / Q000502:physiology; D002471:Cell Transformation, Neoplastic; D018031:Connexin 43 / Q000378:metabolism*; D050719:Crk-Associated Substrate Protein / Q000235:genetics / Q000378:metabolism*; D022001:Focal Adhesions / Q000378:metabolism; D017629:Gap Junctions / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism*
C493842:Bcar1 protein, mouse; D018031:Connexin 43; D050719:Crk-Associated Substrate Protein; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; D014443:Tyrosine; D019061:src-Family Kinases