Mind the Gap; Regulation of Gap Junctional, Intercellular Communication by the Src Oncogene Product and its Effectors

Gap junctions are channels that connect the interiors of neighboring cells and are formed by the connexin (Cx) proteins. A reduction in gap junctional, intercellular communication (GJIC) often correlates with increased growth and neoplastic transformation. Cx43 is a widely expressed connexin which can be phosphorylated by the Sic oncoprotein tyrosine kinase on tyr247 and -265, and this reduces communication. However, Src activates multiple signalling pathways such as the Ras/Raf/Erk and PLC gamma/protein kinase C, which can also phosphorylate Cx43 and interrupt communication. In addition, the Src effector Cas, which has an adaptor function, binds Cx43 to suppress gap junctional communication. In sharp contrast, activation of a different Src effector, the cytoplasmic transcription factor Signal transducer and activator of transcription-3 (Stat3) is not required for the Src-mediated, GJIC suppression. In fact, Stat3 is actually required for the maintenance of gap junctional communication in normal cells with high GJIC.