Am J Physiol Cell Physiol AJP: Heart and Circulatory Physiology
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Am J Physiol Cell Physiol (October 16, 2002). doi:10.1152/ajpcell.00214.2002
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Articles in PresS, published online ahead of print October 16, 2002
Am J Physiol Cell Physiol, 10.1152/ajpcell.00214.2002
Submitted on May 10, 2002
Accepted on October 10, 2002

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

G. T Cottrell1, Rui Lin2, Bonnie J Warn-Cramer2, Alan F Lau2, and Janis M Burt1*

1 Department of Physiology, Arizona Health Sciences Center, University of Arizona, Tucson, AZ, USA
2 Cancer Research Center and the Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, USA

* To whom correspondence should be addressed. E-mail: jburt{at}u.arizona.edu.

Cx43 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, as previous results suggest that channel number is unaffected. Co-expression of v-Src with Cx43-wt but not Cx43-Y247,265F resulted in reduced electrical- and dye-coupling but no change in single channel amplitudes. EGF-treatment of Cx43-wt but not Cx43-S255,279,282A expressing cells 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.




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