Differential involvement of Gα12 and Gα13 in receptor-mediated stress fiber formation
Differential involvement of Gα12 and Gα13 in receptor-mediated stress fiber formation
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DOI：
10.1074/jbc.274.25.17901
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发表时间：
1999-06-18
影响因子：
4.8
通讯作者：
Schultz, G
中科院分区：
文献类型：
--
作者：
Gohla, A;Offermanns, S;Schultz, G
广泛表达的异源三聚体鸟嘌呤核苷酸结合蛋白（G蛋白）G（12）和G（13）已被证明可以激活小的GT3 Rho。Rho刺激导致肌动蛋白细胞骨架的快速重塑和随后的应力纤维形成。我们研究了G（12）或G（13）参与通过各种G（q）/G（11）偶联受体诱导的应力纤维形成。使用来自野生型和G α（q）/G α（11）缺陷小鼠的成纤维细胞系，我们发现，在存在或不存在G α（q）/G α的情况下，凝血酶或溶血磷脂酸的内源性受体以及异源表达的缓激肽B-2、血管加压素V-1A、内皮素ETA和5-羟色胺5-HT 2C受体的激动剂依赖性激活诱导应激纤维形成（11）。通过毒蕈碱M-1和代谢型谷氨酸亚型1 α受体诱导的应力纤维组装依赖于G（q）/G（11）蛋白。G（q）/G（11）偶联的内皮素ETB和血管紧张素AT、A受体的激活不能诱导应力纤维的形成。溶血磷脂酸、B-2和5-HT 2C受体介导的应激纤维形成依赖于G α（13）并涉及表皮生长因子（EGF）受体，而凝血酶、ETA和V-1A受体以EGF受体非依赖性方式通过G α（12）诱导应激纤维积聚。我们的数据表明，许多G（q）/G（11）偶联受体在G α（q）和G α（11）不存在的情况下诱导应力纤维组装，并且这涉及G α（12）或G α（13）/EGF受体介导的途径。
The ubiquitously expressed heterotrimeric guanine nucleotide-binding proteins (G-proteins) G(12) and G(13) have been shown to activate the small GTPase Rho. Rho stimulation leads to a rapid remodeling of the actin cytoskeleton and subsequent stress fiber formation. We investigated the involvement of G(12) or G(13) in stress fiber formation induced through a variety of G(q)/G(11)-coupled receptors. Using fibroblast cell lines derived from wildtype and G alpha(q)/G alpha(11)-deficient mice, we show that agonist-dependent activation of the endogenous receptors for thrombin or lysophosphatidic acid and of the heterologously expressed bradykinin B-2, vasopressin V-1A, endothelin ETA, and serotonin 5-HT2C receptors induced stress fiber formation in either the presence or absence of G alpha(q)/G alpha(11). Stress fiber assembly induced through the muscarinic M-1 and the metabotropic glutamate subtype 1 alpha receptors was dependent on G(q)/G(11) proteins. The activation of the G(q)/G(11)-coupled endothelin ETB and angiotensin AT,A receptors failed to induce stress fiber formation. Lysophosphatidic acid, B-2, and 5-HT2C receptor-mediated stress fiber formation was dependent on G alpha(13) and involved epidermal growth factor (EGF) receptors, whereas thrombin, ETA, and V-1A receptors induced stress fiber accumulation via G alpha(12) in an EGF receptor-independent manner. Our data demonstrate that many G(q)/G(11)-coupled receptors induce stress fiber assembly in the absence of G alpha(q) and G alpha(11) and that this involves either a G alpha(12) or a G alpha(13)/EGF receptor-mediated pathway.