Mind the gap; regulation of gap junctional, intercellular communication by the SRC oncogene product and its effectors
Geletu, M.; Trotman-Grant, A.; Raptis, L.
Anticancer Research 32(10): 4245-4250
2012
ISSN/ISBN: 0250-7005 PMID: 23060544 Document Number: 661045
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 Src oncoprotein tyrosine kinase on tyr247 and -265, and this reduces communication. However, Src activates multiple signalling pathways such as the Ras/Raf/Erk and PLCγ/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.