Tyrosine phosphorylation regulates the adhesions of ras-transformed breast epithelia.
Tyrosine phosphorylation regulates the adhesions of ras-transformed breast epithelia.
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酪氨酸磷酸化调节Ras转化的乳腺上皮菌的粘附。
DOI：
10.1083/jcb.130.2.461
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发表时间：
1995-07
影响因子：
7.8
通讯作者：
BURRIDGE, K
中科院分区：
文献类型：
--
作者：
KINCH, MS;CLARK, GJ;DER, CJ;BURRIDGE, K
转化的上皮细胞通常以成纤维细胞或间充质形态为特征。这些细胞表现出改变的细胞-细胞和细胞-基质相互作用。在这里，我们已经确定的变化，转化上皮细胞的粘附和细胞骨架的相互作用，有助于他们改变形态。使用MCF-10A人乳腺上皮细胞作为模型系统，我们发现ras活化形式的转化的特征在于细胞之间的粘附型连接不太发达，但粘着斑增加。促成转化细胞的修饰的粘附连接的是β-连环蛋白、E-钙粘蛋白和肌动蛋白细胞骨架之间的相互作用减少。ras转化的细胞揭示了许多蛋白质中磷酸酪氨酸的升高，包括β-连环蛋白和p120 Cas。而在正常细胞中，β-连环蛋白被发现与E-钙粘蛋白相关，p120 Cas则没有。在ras转化的细胞中，情况正好相反;酪氨酸磷酸化的p120 Cas，而不是酪氨酸磷酸化的β-连环蛋白，现在在E-钙粘蛋白复合物中检测到。酪氨酸磷酸化的β-连环蛋白也显示出增加的去污剂溶解度，表明与肌动蛋白细胞骨架的关联减少。p120 Cas，无论是否酪氨酸磷酸化，都分配到去污剂可溶性部分中，这表明它在正常或ras转化细胞中都不与肌动蛋白细胞骨架紧密结合。酪氨酸激酶抑制剂降低酪氨酸磷酸化水平，并恢复ras转化细胞的正常上皮形态。特别是，β-连环蛋白的酪氨酸磷酸化减少伴随着与E-钙粘蛋白和去污剂不溶性细胞骨架部分的相互作用增加。这些结果表明，升高的酪氨酸磷酸化的蛋白质，如β-连环蛋白和p120 Cas有助于改变ras转化上皮细胞的粘附连接。
Transformed epithelial cells often are characterized by a fibroblastic or mesenchymal morphology. These cells exhibit altered cell-cell and cell-substrate interactions. Here we have identified changes in the adhesions and cytoskeletal interactions of transformed epithelial cells that contribute to their altered morphology. Using MCF-10A human breast epithelial cells as a model system, we have found that transformation by an activated form of ras is characterized by less developed adherens- type junctions between cells but increased focal adhesions. Contributing to the modified adherens junctions of the transformed cells are decreased interactions among beta-catenin, E-cadherin, and the actin cytoskeleton. The ras-transformed cells reveal elevated phosphotyrosine in many proteins, including beta-catenin and p120 Cas. Whereas in the normal cells beta-catenin is found in association with E- cadherin, p120 Cas is not. In the ras-transformed cells, the situation is reversed; tyrosine-phosphorylated p120 Cas, but not tyrosine- phosphorylated beta-catenin, now is detected in E-cadherin complexes. The tyrosine-phosphorylated beta-catenin also shows increased detergent solubility, suggesting a decreased association with the actin cytoskeleton. p120 Cas, whether tyrosine phosphorylated or not, partitions into the detergent soluble fraction, suggesting that it is not tightly bound to the actin cytoskeleton in either the normal or ras- transformed cells. Inhibitors of tyrosine kinases decrease the level of tyrosine phosphorylation and restore a normal epithelial morphology to the ras-transformed cells. In particular, decreased tyrosine phosphorylation of beta-catenin is accompanied by increased interaction with both E-cadherin and the detergent insoluble cytoskeletal fraction. These results suggest that elevated tyrosine phosphorylation of proteins such as beta-catenin and p120 Cas contribute to the altered adherens junctions of ras-transformed epithelia.
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DOI：
10.1083/jcb.125.6.1341
发表时间：
1994-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Näthke IS;Hinck L;Swedlow JR;Papkoff J;Nelson WJ
通讯作者：
Nelson WJ
DOI：
10.1073/pnas.82.19.6576
发表时间：
1985-01-01
影响因子：
11.1
作者：
MAHER, PA;PASQUALE, EB;SINGER, SJ
通讯作者：
SINGER, SJ
DOI：
10.1006/scel.1993.1021
发表时间：
1993-06-01
期刊：
Seminars in cell biology
影响因子：
--
作者：
Nagafuchi, A;Tsukita, S;Takeichi, M
通讯作者：
Takeichi, M
DOI：
10.1073/pnas.91.7.2790
发表时间：
1994-03-29
影响因子：
11.1
作者：
NORMANNO, N;SELVAM, MP;SALOMON, DS
通讯作者：
SALOMON, DS
影响因子：
5.3
作者：
REYNOLDS, AB;ROESEL, DJ;PARSONS, JT
通讯作者：
PARSONS, JT