Mechanism of v-Src- and mitogen-activated protein kinase-induced reduction of gap junction communication

• Published in: American Journal of Physiology: Cell Physiology Vol. 284; no. 2; pp. C511 - C520
• Main Authors: Cottrell, G. Trevor, Lin, Rui, Warn-Cramer, Bonnie J, Lau, Alan F, Burt, Janis M
• Format: Journal Article
• Language: English
• Published: United States 01.02.2003
• Subjects: Animals; Cell Communication - physiology; Cells, Cultured; Connexin 43 - deficiency; Connexin 43 - genetics; Epidermal Growth Factor - pharmacology; Eukaryotic Cells - drug effects; Eukaryotic Cells - metabolism; Gap Junctions - drug effects; Gap Junctions - metabolism; Isoquinolines; Membrane Potentials - drug effects; Membrane Potentials - genetics; Mice; Mice, Knockout; Mitogen-Activated Protein Kinases - metabolism; Mutation - drug effects; Mutation - physiology; Oncogene Protein pp60(v-src) - metabolism; Phosphorylation - drug effects; Pyrimidines - pharmacology; Quaternary Ammonium Compounds - pharmacology; Tyrosine - metabolism
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.00214.2002

1  Department of Physiology, Arizona Health Sciences Center, University of Arizona, Tucson, Arizona 85724; and 2  Cancer Research Center and Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii 96813 Connexin (Cx)43 gap junction channels are phosphorylated by numerous protein kinases, with the net effect typically being a reduction in gap junction communication (GJC). This reduction must result from a decrease in channel open probability, unitary conductance, or permselectivity, because previous results suggest that channel number is unaffected. Coexpression of v-Src with wild-type Cx43 (Cx43-wt) but not Cx43 with tyrosine to phenylalanine substitutions at 247 and 265 (Cx43-Y247,265F) resulted in reduced electrical and dye coupling but no change in single-channel amplitudes. EGF treatment of cells expressing Cx43-wt but not Cx43 with serine to alanine substitutions at 255, 279, and 282 (Cx43-S255,279,282A) resulted in reduced GJC, also with no change in single-channel amplitude. Dye coupling was reduced to a far greater extent than electrical coupling, suggesting that channel selectivity was also altered but with minimal effect on unitary conductance. The absence of Src- and MAPK-induced reductions in single-channel amplitude suggests that the decreases in GJC induced by these kinases result from reduced channel open probability and possibly altered selectivity. connexins; growth factors; dye permeability; electrophysiology; epidermal growth factor