v-Src requires Ras signaling for the suppression of gap junctional intercellular communication
v-Src requires Ras signaling for the suppression of gap junctional intercellular communication
复制标题
DOI：
10.1038/sj.onc.1209263
复制
发表时间：
2006-04-13
期刊：
影响因子：
8
通讯作者：
Hamaguchi, M
中科院分区：
文献类型：
--
作者：
Ito, S;Ito, Y;Hamaguchi, M
v-Src的细胞转化导致间隙连接细胞间通讯（GJIC）的抑制。虽然缝隙连接蛋白43（Cx43）的酪氨酸磷酸化似乎是抑制所必需的，但其他信号传导的参与仍不清楚。我们研究了Ras信号在v-Src抑制GJIC中的作用。S17 N Ras或mtGap 1 m的条件性表达显著恢复了v-Src转化细胞中的GJIC。尽管S17 N Ras或mtGap 1 m的表达显著降低了活性Ras的水平，但包括Cx43在内的细胞蛋白的酪氨酸磷酸化保持不变。类似地，用Ras法尼基转移酶抑制剂manumycin A处理v-Src-cystomed细胞，恢复了GJIC，而Cx43的酪氨酸磷酸化保持不变。因此，这些结果强烈表明，除了Cx43磷酸化，Ras信号传导的组成性激活是V-Src抑制GJIC所必需的。
Cell transformation by v-Src causes suppression of gap junctional intercellular communication (GJIC). Although tyrosine phosphorylation of connexin43 (Cx43), a gap junctional component, appears to be necessary for the suppression, involvement of other signaling remains unclear. We investigated the role of Ras signaling in the suppression of GJIC by v-Src. Conditional expression of either S17N Ras or mtGap1m dramatically recovered GJIC in v-Src-transformed cells. Although expression of S17N Ras or mtGap1m substantially decreased the levels of active Ras, tyrosine phosphorylation of cellular proteins including Cx43 remained unchanged. Similarly, treatment of v-Src-transfomed cells with a Ras farnesyltransferase inhibitor, manumycin A, restored GJIC, whereas tyrosine phosphorylation of Cx43 remained unchanged. Thus, these results strongly suggest that, in addition to Cx43 phosphorylation, constitutive activation of Ras signaling is required for the suppression of GJIC by v-Src.