Cottrell G Trevor, Lin Rui, Warn-Cramer Bonnie J, Lau Alan F, Burt Janis M
Department of Physiology, Arizona Health Sciences Center, University of Arizona, Tucson, Arizona 85724, USA.
Am J Physiol Cell Physiol. 2003 Feb;284(2):C511-20. doi: 10.1152/ajpcell.00214.2002. Epub 2002 Oct 16.
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.
连接蛋白（Cx）43间隙连接通道被多种蛋白激酶磷酸化，其总体效应通常是间隙连接通讯（GJC）减少。这种减少必定是由于通道开放概率、单位电导或通透选择性降低所致，因为先前的结果表明通道数量不受影响。v-Src与野生型Cx43（Cx43-wt）共表达，但与在247和265位酪氨酸被苯丙氨酸取代的Cx43（Cx43-Y247,265F）共表达时，电偶联和染料偶联减少，但单通道幅度无变化。用表皮生长因子（EGF）处理表达Cx43-wt的细胞，但不处理在255、279和282位丝氨酸被丙氨酸取代的Cx43（Cx43-S255,279,282A），导致GJC减少，单通道幅度同样无变化。染料偶联的减少程度远大于电偶联，这表明通道选择性也发生了改变，但对单位电导的影响最小。Src和丝裂原活化蛋白激酶（MAPK）诱导的单通道幅度未降低，这表明这些激酶诱导的GJC减少是由于通道开放概率降低以及可能的选择性改变所致。
