Maintaining connexin43 gap junctional communication in v-Src cells does not alter growth properties associated with the transformed phenotype.
Loss of connexin expression and/or gap junctional communication (GJC) has been correlated with increased rates of cell growth in tumor cells compared to their normal communication-competent counterparts. Conversely, reduced rates of cell growth have been observed in tumor cells that are induced to express exogenous connexins and re-establish GJC. It is not clear how this putative growth-suppressive effect of the connexin proteins is mediated and some data has suggested that this function may be independent of GJC. In mammalian cells that express v-Src, connexin43 (Cx43) is phosphorylated on Tyr247 and Tyr265 and this results in a dramatic disruption of GJC. Cells that express a Cx43 mutant with phenylalanine mutations at these tyrosine sites form functional gap junctions that, unlike junctions formed by wild type Cx43, remain functional in cells that co-express v-Src. These cells still appear transformed; however, it is not known whether their ability to maintain GJC prevents the loss of growth restraints that confine "normal" cells, such as the inability to grow in an anchorage-independent manner or to form foci. In these studies, we have examined some of the growth properties of cells with Cx43 gap junctions that remain communication-competent in the presence of the co-expressed v-Src oncoprotein.
Warn-Cramer
Bonnie J
BJ
Cancer Research Center of Hawaii, University of Hawaii at Manoa, Honolulu, HI 96813, USA. bonnie@crch.hawaii.edu
Lin
Rui
R
Martyn
Kendra
K
Guyette
Carrie V
CV
Lau
Alan F
AF
D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D018031:Connexin 43 / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D017629:Gap Junctions / Q000378:metabolism*; D007365:Intercellular Junctions / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D015688:Oncogene Protein pp60(v-src) / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats
D018031:Connexin 43; D015688:Oncogene Protein pp60(v-src)