Mechanism of v-Src- and mitogen-activated protein kinase-induced reduction of gap junction communication.
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.
Cottrell
G Trevor
GT
Department of Physiology, Arizona Health Sciences Center, University of Arizona, Tucson, Arizona 85724, USA.
Lin
Rui
R
Warn-Cramer
Bonnie J
BJ
Lau
Alan F
AF
Burt
Janis M
JM
D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D002478:Cells, Cultured; D018031:Connexin 43 / Q000172:deficiency* / Q000235:genetics; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005057:Eukaryotic Cells / Q000187:drug effects / Q000378:metabolism*; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism*; D007546:Isoquinolines; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009154:Mutation / Q000187:drug effects / Q000502:physiology; D015688:Oncogene Protein pp60(v-src) / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism
C411962:2-(4-nitro-2,1,3-benzoxadiazol-7-yl)aminoethyl-trimethylammonium; C412373:AG 1879; D018031:Connexin 43; D007546:Isoquinolines; D011743:Pyrimidines; D000644:Quaternary Ammonium Compounds; D014443:Tyrosine; D004815:Epidermal Growth Factor; C017475:lucifer yellow; D015688:Oncogene Protein pp60(v-src); D020928:Mitogen-Activated Protein Kinases