Ito S, Ito Y, Senga T, Hattori S, Matsuo S, Hamaguchi M
Division of Cancer Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Oncogene. 2006 Apr 13;25(16):2420-4. doi: 10.1038/sj.onc.1209263.
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.
v-Src介导的细胞转化会导致间隙连接细胞间通讯（GJIC）受到抑制。尽管间隙连接成分连接蛋白43（Cx43）的酪氨酸磷酸化似乎是这种抑制所必需的，但其他信号传导的参与情况仍不清楚。我们研究了Ras信号传导在v-Src抑制GJIC中的作用。条件性表达S17N Ras或mtGap1m可显著恢复v-Src转化细胞中的GJIC。尽管S17N Ras或mtGap1m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水平保持不变。同样，用Ras法尼基转移酶抑制剂马马霉素A处理v-Src转化细胞可恢复GJIC，而Cx43的酪氨酸磷酸化水平保持不变。因此，这些结果强烈表明，除了Cx43磷酸化外，Ras信号传导的组成性激活也是v-Src抑制GJIC所必需的。
