Vinculin phosphorylation differentially regulates mechanotransduction at cell-cell and cell-matrix adhesions.
Vinculin phosphorylation differentially regulates mechanotransduction at cell-cell and cell-matrix adhesions.
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Vinculin磷酸化差异地调节了细胞 - 细胞和细胞矩阵粘附处的机械转导。
DOI：
10.1083/jcb.201309092
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发表时间：
2014-04-28
期刊：
影响因子：
--
通讯作者：
DeMali KA
中科院分区：
文献类型：
--
作者：
Bays JL;Peng X;Tolbert CE;Guilluy C;Angell AE;Pan Y;Superfine R;Burridge K;DeMali KA
残基Y822上的胰蛋白酶磷酸化是细胞响应钙粘蛋白而不是整合素上的张力而硬化所必需的。细胞在其整个生命周期中都会受到机械力的作用。骨钙素对于传递这些力是至关重要的，但它如何在细胞-细胞和细胞-基质粘附中实现其独特的功能仍然没有答案。在这里，我们显示黏着斑蛋白是磷酸化的Y822在细胞-细胞，但不是细胞-基质，粘附。Y822磷酸化升高时，部队被施加到E-钙粘蛋白，并需要黏着斑蛋白整合到钙粘蛋白复合物。突变Y822 F消除了这些活动，并防止细胞对E-钙粘蛋白的作用力作出反应。与此相反，Y822磷酸化是不需要的黏着斑蛋白功能的细胞基质粘附，包括整合素诱导的细胞硬化。最后，施加到E-钙粘蛋白的力激活Abelson（Abl）酪氨酸激酶磷酸化黏着斑蛋白; Abl抑制模仿黏着斑蛋白磷酸化的损失。这些数据揭示了一个意想不到的调节机制，其中黏着斑蛋白Y822磷酸化决定了钙粘蛋白是否传递力，并为粘连的共享组分如何产生生物学上不同的功能提供了一个范例。
Vinculin phosphorylation on residue Y822 is necessary for cell stiffening in response to tension on cadherins but not integrins. Cells experience mechanical forces throughout their lifetimes. Vinculin is critical for transmitting these forces, yet how it achieves its distinct functions at cell–cell and cell–matrix adhesions remains unanswered. Here, we show vinculin is phosphorylated at Y822 in cell–cell, but not cell–matrix, adhesions. Phosphorylation at Y822 was elevated when forces were applied to E-cadherin and was required for vinculin to integrate into the cadherin complex. The mutation Y822F ablated these activities and prevented cells from stiffening in response to forces on E-cadherin. In contrast, Y822 phosphorylation was not required for vinculin functions in cell–matrix adhesions, including integrin-induced cell stiffening. Finally, forces applied to E-cadherin activated Abelson (Abl) tyrosine kinase to phosphorylate vinculin; Abl inhibition mimicked the loss of vinculin phosphorylation. These data reveal an unexpected regulatory mechanism in which vinculin Y822 phosphorylation determines whether cadherins transmit force and provides a paradigm for how a shared component of adhesions can produce biologically distinct functions.
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影响因子：
2.9
作者：
Lessey EC;Guilluy C;Burridge K
通讯作者：
Burridge K
DOI：
10.1083/jcb.201001149
发表时间：
2010-06-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
le Duc Q;Shi Q;Blonk I;Sonnenberg A;Wang N;Leckband D;de Rooij J
通讯作者：
de Rooij J
影响因子：
4
作者：
Huveneers, Stephan;de Rooij, Johan
通讯作者：
de Rooij, Johan
影响因子：
3.3
作者：
Owens, DW;McLean, GW;Brunton, VG
通讯作者：
Brunton, VG
影响因子：
4
作者：
Goldyn, Alexandra M.;Rioja, Borja Aragues;Kemkemer, Ralf
通讯作者：
Kemkemer, Ralf