v-Src tyrosine phosphorylation of connexin43: regulation of gap junction communication and effects on cell transformation.
v-Src tyrosine phosphorylation of connexin43: regulation of gap junction communication and effects on cell transformation.
复制标题
connexin43 的 v-Src 酪氨酸磷酸化：间隙连接通讯的调节和对细胞转化的影响。
DOI：
10.1080/15419060600848516
复制
发表时间：
2006
影响因子：
--
通讯作者：
Warn-Cramer,BonnieJ
中科院分区：
文献类型：
--
作者：
Lin,Rui;Martyn,KendraD;Guyette,CarrieV;Lau,AlanF;Warn-Cramer,BonnieJ
致癌酪氨酸激酶v-Src使Y247和Y265上的连接蛋白43（Cx43）磷酸化，并抑制Cx43间隙连接通讯（GJC），即细胞间离子和代谢物交换的过程。为了测试由酪氨酸磷酸化诱导的Cx43上的负电荷的作用，我们表达了在Y247或Y265处具有谷氨酸取代的Cx43。Cx43 Y247 E或Cx43 Y265 E通道在Cx43敲除的成纤维细胞中是功能性的，表明在Cx43上引入负电荷不太可能是GJC的v-Src破坏的机制。细胞共表达v-Src和三重丝氨酸丙氨酸突变体，Cx43 S255/279/282 A，证实了Cx43的促分裂原活化蛋白（MAP）激酶磷酸化对于v-Src诱导的GJC破坏是不需要的，酪氨酸磷酸化是足够的。此外，v-Src细胞含有v-Src-抗性间隙连接，Cx43 Y247/265 F，显示细胞迁移，粘附和增殖的特性类似于Cx43 wt/v-Src细胞，这表明Cx43酪氨酸磷酸化和GJC的破坏不参与这些转化的细胞特性。
The oncogenic tyrosine kinase, v-Src, phosphorylates connexin43 (Cx43) on Y247 and Y265 and inhibits Cx43 gap junctional communication (GJC), the process of intercellular exchange of ions and metabolites. To test the role of a negative charge on Cx43 induced by tyrosine phosphorylation, we expressed Cx43 with glutamic acid substitutions at Y247 or Y265. The Cx43Y247E or Cx43Y265E channels were functional in Cx43 knockout fibroblasts, indicating that introducing a negative charge on Cx43 was not likely the mechanism for v-Src disruption of GJC. Cells coexpressing v-Src and the triple serine to alanine mutant, Cx43S255/279/282A, confirmed that mitogen-activated protein (MAP) kinase phosphorylation of Cx43 was not required for v-Src-induced disruption of GJC and that tyrosine phosphorylation was sufficient. In addition, v-Src cells containing v-Src-resistant gap junctions, Cx43Y247/265F, displayed properties of cell migration, adhesion, and proliferation similar to Cx43wt/v-Src cells, suggesting that Cx43 tyrosine phosphorylation and disruption of GJC are not involved in these transformed cell properties.