Goldberg G S, Lau A F
Molecular Carcinogenesis Program, University of Hawaii at Manoa, Honolulu 96813.
Biochem J. 1993 Nov 1;295 ( Pt 3)(Pt 3):735-42. doi: 10.1042/bj2950735.
Connexin43 phosphorylation was analysed in non-transformed and pp60v-src-transformed Rat-1 fibroblasts. Connexin43 appeared to be the primary connexin expressed in these cells. Although gap-junctional communication was disrupted in pp60v-src-transformed cells, they contained more connexin43 protein and RNA than their non-transformed counterpart. Connexin43 was phosphorylated within minutes of its synthesis in both cell types and appeared to be degraded while in the phosphorylated state. Phosphopeptide and phosphoamino acid analyses suggested that connexin43 in both cell types contained at least five fragments with serine phosphorylation. The major difference in connexin43 phosphorylation between the pp60v-src-transformed and non-transformed cells was that, whereas approx. 70% of the phosphorylated connexin43 in the former contained phosphotyrosine, this phosphoamino acid was not detected in connexin43 isolated from the latter cells. These data support the hypothesis that phosphorylation of connexin43 on tyrosine is critical for the blockade of gap-junctional communication which occurs concomitantly with transformation by the pp60v-src oncogene.
在未转化的和pp60v-src转化的大鼠1型成纤维细胞中分析了连接蛋白43的磷酸化情况。连接蛋白43似乎是这些细胞中主要表达的连接蛋白。尽管在pp60v-src转化的细胞中缝隙连接通讯被破坏，但它们比未转化的对应细胞含有更多的连接蛋白43蛋白和RNA。在两种细胞类型中，连接蛋白43在合成后几分钟内就被磷酸化，并且在磷酸化状态时似乎会被降解。磷酸肽和磷酸氨基酸分析表明，两种细胞类型中的连接蛋白43至少含有五个丝氨酸磷酸化片段。pp60v-src转化细胞和未转化细胞之间连接蛋白43磷酸化的主要差异在于，前者中约70%的磷酸化连接蛋白43含有磷酸酪氨酸，而从后者细胞中分离的连接蛋白43中未检测到这种磷酸氨基酸。这些数据支持这样的假说，即连接蛋白43酪氨酸磷酸化对于缝隙连接通讯的阻断至关重要，而缝隙连接通讯的阻断与pp60v-src癌基因转化同时发生。
