Matrix-dependent Tiam1/Rac signaling in epithelial cells promotes either cell-cell adhesion or cell migration and is regulated by phosphatidylinositol 3-kinase.
Matrix-dependent Tiam1/Rac signaling in epithelial cells promotes either cell-cell adhesion or cell migration and is regulated by phosphatidylinositol 3-kinase.
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DOI：
10.1083/jcb.143.5.1385
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发表时间：
1998-11-30
期刊：
影响因子：
--
通讯作者：
Collard JG
中科院分区：
文献类型：
--
作者：
Sander EE;van Delft S;ten Klooster JP;Reid T;van der Kammen RA;Michiels F;Collard JG
我们之前证明，Rac 激活剂 Tiam1 和组成型活性 V12Rac 均可促进上皮 Madin Darby 犬肾 (MDCK) 细胞中 E-钙粘蛋白介导的细胞间粘附。此外，Tiam1 和 V12Rac 通过恢复 E-钙粘蛋白介导的细胞间粘附来抑制 Ras 转化的成纤维细胞 MDCK-f3 细胞的侵袭。在这里，我们表明 Tiam1/Rac 诱导的细胞反应依赖于细胞底物。在纤连蛋白和层粘连蛋白 1 上，Tiam1/Rac 信号传导通过恢复 E-钙粘蛋白介导的细胞间粘附来抑制 MDCK-f3 细胞的迁移。然而，在不同的胶原蛋白上，Tiam1 和 V12Rac 的表达在防止 E-钙粘蛋白粘附形成的条件下促进运动行为。在非运动细胞中，Tiam1 存在于粘附连接中，而 Tiam1 定位于迁移细胞的片层中。 Tiam1 的 Rac 激活水平（通过与谷胱甘肽-S-转移酶 - PAK 蛋白的结合来确定）在纤连蛋白或 I 型胶原上相似，这表明 Tiam1/Rac 信号复合物的定位决定了底物依赖性细胞反应。 Tiam1 激活 Rac 需要 PI3 激酶活性。此外，Tiam1（而非 V12Rac）诱导的迁移以及 E-钙粘蛋白介导的细胞间粘附均依赖于 PI3 激酶，表明 PI3 激酶在 Tiam1 和 Rac 的上游发挥作用。
We previously demonstrated that both Tiam1, an activator of Rac, and constitutively active V12Rac promote E-cadherin–mediated cell–cell adhesion in epithelial Madin Darby canine kidney (MDCK) cells. Moreover, Tiam1 and V12Rac inhibit invasion of Ras-transformed, fibroblastoid MDCK-f3 cells by restoring E-cadherin–mediated cell–cell adhesion. Here we show that the Tiam1/Rac-induced cellular response is dependent on the cell substrate. On fibronectin and laminin 1, Tiam1/Rac signaling inhibits migration of MDCK-f3 cells by restoring E-cadherin–mediated cell– cell adhesion. On different collagens, however, expression of Tiam1 and V12Rac promotes motile behavior, under conditions that prevent formation of E-cadherin adhesions. In nonmotile cells, Tiam1 is present in adherens junctions, whereas Tiam1 localizes to lamellae of migrating cells. The level of Rac activation by Tiam1, as determined by binding to a glutathione-S-transferase– PAK protein, is similar on fibronectin or collagen I, suggesting that rather the localization of the Tiam1/Rac signaling complex determines the substrate-dependent cellular responses. Rac activation by Tiam1 requires PI3-kinase activity. Moreover, Tiam1- but not V12Rac-induced migration as well as E-cadherin–mediated cell– cell adhesion are dependent on PI3-kinase, indicating that PI3-kinase acts upstream of Tiam1 and Rac.
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影响因子：
56.9
作者：
Kheradmand, F;Werner, E;Werb, Z
通讯作者：
Werb, Z
影响因子：
64.8
作者：
MANSER, E;LEUNG, T;LIM, L
通讯作者：
LIM, L
影响因子：
64.5
作者：
Kolanus, W;Nagel, W;Seed, B
通讯作者：
Seed, B
影响因子：
7.8
作者：
Michiels, F;Stam, JC;Hordijk, PL;vanderKammen, RA;RuulsVanStalle, L;Feltkamp, CA;Collard, JG
通讯作者：
Collard, JG
DOI：
10.1083/jcb.141.5.1147
发表时间：
1998-06-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Allen WE;Zicha D;Ridley AJ;Jones GE
通讯作者：
Jones GE