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首页> 外文期刊>Molecular and Cellular Biology >Role of Phospholipase Cγ1 in Cell Spreading Requires Association with a β-Pix/GIT1-Containing Complex, Leading to Activation of Cdc42 and Rac1
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Role of Phospholipase Cγ1 in Cell Spreading Requires Association with a β-Pix/GIT1-Containing Complex, Leading to Activation of Cdc42 and Rac1

机译：磷脂酶Cγ1在细胞扩散中的作用需要与包含β-Pix/ GIT1的复合物缔合，从而导致Cdc42和Rac1活化

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The significance of multiprotein signaling complexes in cell motility is becoming increasingly important. We have previously shown that phospholipase Cγ1 (PLCγ1) is critical for integrin-mediated cell spreading and motility (N. Jones et al., J. Cell Sci. 118:2695-2706, 2005). In the current study we show that, on a basement membrane-type matrix, PLCγ1 associates with the adaptor protein GIT1 and the Rac1/Cdc42 guanine exchange factor β-Pix; GIT1 and β-Pix form tight complexes independently of PLCγ1. The association of PLCγ1 with the complex requires both GIT1 and β-Pix and the specific array region (γSA) of PLCγ1. Mutations of PLCγ1 within the γSA region reveal that association with this complex is essential for the phosphorylation of PLCγ1 and the progression to an elongated morphology after integrin engagement. Short interfering RNA (siRNA) depletion of either β-Pix or GIT1 inhibited cell spreading in a fashion similar to that seen with siRNA against PLCγ1. Furthermore, siRNA depletion of PLCγ1, β-Pix, or GIT1 inhibited Cdc42 and Rac1 activation, while constitutively active forms of Cdc42 or Rac1, but not RhoA, were able to rescue the elongation of these cells. Signaling of the PLCγ1/GIT1/β-Pix complex to Cdc42/Rac1 was found to involve the activation of calpains, calcium-dependent proteases. Therefore, we propose that the association of PLCγ1 with complexes containing GIT1 and β-Pix is essential for its role in integrin-mediated cell spreading and motility. As a component of this complex, PLCγ1 is also involved in the activation of Cdc42 and Rac1.
机译：多蛋白信号复合物在细胞运动中的重要性变得越来越重要。先前我们已经表明磷脂酶Cγ1（PLCγ1）对于整联蛋白介导的细胞扩散和运动至关重要（N. Jones et al。，J. Cell Sci。118：2695-2706，2005）。在当前的研究中，我们表明，在基底膜型基质上，PLCγ1与衔接蛋白GIT1和Rac1 / Cdc42鸟嘌呤交换因子β-Pix缔合。 GIT1和β-Pix独立于PLCγ1形成紧密的复合物。 PLCγ1与复合物的结合需要GIT1和β-Pix以及PLCγ1的特定阵列区域（γSA）。 γSA区域内PLCγ1的突变表明，与这种复合物的缔合对于整合素结合后PLCγ1的磷酸化以及向伸长形态的发展至关重要。 β-Pix或GIT1的短暂干扰RNA（siRNA）耗竭以类似于针对PLCγ1的siRNA所见的方式抑制细胞扩散。此外，PLCγ1，β-Pix或GIT1的siRNA耗竭抑制了Cdc42和Rac1的激活，而Cdc42或Rac1的组成型活性形式（而非RhoA）能够挽救这些细胞的伸长。发现PLCγ1/ GIT1 /β-Pix复合物向Cdc42 / Rac1的信号传导涉及钙蛋白酶，钙依赖性蛋白酶的活化。因此，我们认为PLCγ1与包含GIT1和β-Pix的复合物的结合对于其在整联蛋白介导的细胞扩散和运动中的作用至关重要。作为该复合物的组成部分，PLCγ1也参与了Cdc42和Rac1的激活。

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