p120 catenin-associated Fer and Fyn tyrosine kinases regulate β-catenin Tyr-142 phosphorylation and β-catenin-α-catenin interaction
p120 catenin-associated Fer and Fyn tyrosine kinases regulate β-catenin Tyr-142 phosphorylation and β-catenin-α-catenin interaction
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DOI：
10.1128/mcb.23.7.2287-2297.2003
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发表时间：
2003-04-01
影响因子：
5.3
通讯作者：
Duñach, M
中科院分区：
文献类型：
--
作者：
Piedra, J;Miravet, S;Duñach, M
β-连环蛋白通过其与E-钙粘蛋白和α-连环蛋白的相互作用在粘附连接的形成中具有关键作用。我们发现β-连环蛋白与α-连环蛋白的相互作用受β-连环蛋白Tyr-142磷酸化的调节。该残基可以在体外被Fer或Fyn酪氨酸激酶磷酸化。将这些激酶转染到上皮细胞中破坏了两种连环蛋白之间的关联。我们还研究了这些激酶是否参与调节这种相互作用的K-ras。在肠上皮IEC 18细胞中产生K-ras癌基因的稳定转染子，其相对于对照克隆显示出很少的α-连环蛋白-β-连环蛋白缔合;这种作用伴随着增加的Tyr-142磷酸化和Fer和Fyn激酶的活化。如Fer所报道的，Fyn激酶与p120连环蛋白组成性结合; K-ras的表达诱导p120连环蛋白在酪氨酸残基上的磷酸化，增加其对E-钙粘蛋白的亲和力，从而促进Fyn与粘附连接复合物的结合。是的，酪氨酸激酶也结合p120连环蛋白，但仅在激活后，并刺激Fer和Fyn酪氨酸激酶。这些结果表明，p120连环蛋白作为一个对接蛋白，促进激活的Fer/Fyn酪氨酸激酶的是，并证明了这些p120连环蛋白相关激酶的β-连环蛋白-α-连环蛋白相互作用的调节中的作用。
beta-Catenin has a key role in the formation of adherens junction through its interactions with E-cadherin and alpha-catenin. We show here that interaction of beta-catenin with alpha-catenin is regulated by the phosphorylation of beta-catenin Tyr-142. This residue can be phosphorylated in vitro by Fer or Fyn tyrosine kinases. Transfection of these kinases to epithelial cells disrupted the association between both catenins. We have also examined whether these kinases are involved in the regulation of this interaction by K-ras. Stable transfectants of the K-ras oncogene in intestinal epithelial IEC18 cells were generated which show little alpha-catenin-beta-catenin association with respect to control clones; this effect is accompanied by increased Tyr-142 phosphorylation and activation of Fer and Fyn kinases. As reported for Fer, Fyn kinase is constitutively bound to p120 catenin; expression of K-ras induces the phosphorylation of p120 catenin on tyrosine residues increasing its affinity for E-cadherin and, consequently, promotes the association of Fyn with the adherens junction complex. Yes tyrosine kinase also binds to p120 catenin but only upon activation, and stimulates Fer and Fyn tyrosine kinases. These results indicate that p120 catenin acts as a docking protein facilitating the activation of Fer/Fyn tyrosine kinases by Yes and demonstrate the role of these p120 catenin-associated kinases in the regulation of beta-catenin-alpha-catenin interaction.