Fibronectin rigidity response through Fyn and p130Cas recruitment to the leading edge
Fibronectin rigidity response through Fyn and p130Cas recruitment to the leading edge
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DOI：
10.1091/mbc.e05-12-1161
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发表时间：
2006-06-01
影响因子：
3.3
通讯作者：
Sheetz, Michael P.
中科院分区：
文献类型：
--
作者：
Kostic, Ana;Sheetz, Michael P.
细胞在细胞外基质上的运动主要取决于基质的刚性，这影响细胞粘附和焦点接触的形成。受体样蛋白酪氨酸磷酸酶α（RPTP α）和α（v）β（3）整联蛋白在前缘形成刚性响应复合物。在这里，我们表明，通过增加扩散和增长的刚性反应与前沿招聘的Fyn，但不是内源性的c-Src。Fyn的募集需要N-末端附近的棕榈酰化位点，并且将该位点添加到c-Src使其能够支持刚性反应。在所有情况下，刚性反应与Src家族激酶的募集相关，以早期粘连。Fyn和c-Src的拉伸激活底物p130 Cas也是刚性反应所需的，并且在Fyn依赖性过程的前沿被磷酸化。纤连蛋白刚性反应的一个可能机制涉及p130 Cas的力依赖性Fyn磷酸化与刚性依赖性位移。在较软的表面上，随着Fyn从p130 Cas的更大位移，将存在更少的磷酸化。这些研究强调了力和纳米级运动在细胞生长和功能中的重要性。
Cell motility on extracellular matrices critically depends on matrix rigidity, which affects cell adhesion and formation of focal contacts. Receptor-like protein tyrosine phosphatase alpha (RPTP alpha) and the alpha(v)beta(3) integrin form a rigidity-responsive complex at the leading edge. Here we show that the rigidity response through increased spreading and growth correlates with leading edge recruitment of Fyn, but not endogenous c-Src. Recruitment of Fyn requires the palmitoylation site near the N-terminus and addition of that site to c-Src enables it to support a rigidity response. In all cases, the rigidity response correlates with the recruitment of the Src family kinase to early adhesions. The stretch-activated substrate of Fyn and c-Src, p130Cas, is also required for a rigidity response and it is phosphorylated at the leading edge in a Fyn-dependent process. A possible mechanism for the fibronectin rigidity response involves force-dependent Fyn phosphorylation of p130Cas with rigidity-dependent displacement. With the greater displacement of Fyn from p130Cas on softer surfaces, there will be less phosphorylation. These studies emphasize the importance of force and nanometer-level movements in cell growth and function.