Specific involvement of G proteins in regulation of serum response factor-mediated gene transcription by different receptors
Specific involvement of G proteins in regulation of serum response factor-mediated gene transcription by different receptors
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DOI：
10.1074/jbc.273.42.27118
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发表时间：
1998-10-16
影响因子：
4.8
通讯作者：
Wu, DQ
中科院分区：
文献类型：
--
作者：
Mao, JH;Yuan, HD;Wu, DQ
在转染的NIH 3 T3细胞和来自缺乏G α（q）和G α（11）的小鼠的细胞系中，研究了G蛋白亚基和G蛋白偶联受体对血清反应因子（SRF）介导的基因转录的调节。我们发现G（q）和G（12）类G蛋白的α亚基的组成型活性形式，包括G α（q）、G α（11）、G α（14）、G α（16）、G α（12）和G α（13），可以激活NIH 3 T3细胞中的SRF。我还发现，1型毒蕈碱受体（m1 R）和α（1）-肾上腺素能受体（AR）介导的SRF激活仅依赖于G α（q/11），而凝血酶、溶血磷脂酸（LPA）、血栓烷A2和内皮素的受体可在G α不存在的情况下激活SRF（q/11）。此外，RGS 12而不是RGS 2、RGS 4或Axin能够抑制G α（12）和G α（13）介导的SRF激活。而RGS 12，而不是其他RGS蛋白，在G α（q/11）缺陷细胞中阻断凝血酶和LPA介导的SRF激活。因此，凝血酶、LPA、血栓烷A2和内皮素受体可能能够与G α偶联（12/13）。相反，包括β（2）-和α（2）-AR、m2 R、1型和2型多巴胺受体、1型和2型血管紧张素受体以及白细胞介素-8受体在内的受体在存在或不存在G α（q/11）的情况下不能激活SRF，表明这些受体不能与G（12）或G（q）类的内源性G蛋白偶联。
Regulation of serum response factor (SRF)-mediated gene transcription by G protein subunits and G protein-coupled receptors was investigated in transfected NIH3T3 cells and in a cell line that was derived from mice lacking G alpha(q) and G alpha(11). We found that the constitutively active forms of the alpha subunits of the G(q) and G(12) class of G proteins, including G alpha(q), G alpha(11), G alpha(14), G alpha(16), G alpha(12), and G alpha(13), can activate SRF in NIH3T3 cells. me also found that the type 1 muscarinic receptor (m1R) and alpha(1)-adrenergic receptor (AR)-mediated SRF activation is exclusively dependent on G alpha(q/11), while the receptors for thrombin, lysophosphatidic acid (LPA), thromboxane A2, and endothelin can activate SRF in the absence of G alpha(q/11). Moreover, RGS12 but not RGS2, RGS4, or Axin was able to inhibit G alpha(12) and G alpha(13)-mediated SRF activation. And RGS12, but not other RGS proteins, blocked thrombin- and LPA-mediated SRF activation in the G alpha(q/11)-deficient cells. Therefore, the thrombin, LPA, thromboxane A2, and endothelin receptors may be able to couple to G alpha(12/13). On the contrary, receptors including beta(2)- and alpha(2)-ARs, m2R, the dopamine receptors type 1 and 2, angiotensin receptors types 1 and 2, and interleukin-8 receptor could not activate SRF in the presence or absence of G alpha(q/11), suggesting that these receptors cannot couple to endogenous G proteins of the G(12) or G(q) classes.