N-terminal Short Sequences of α Subunits of the G12Family Determine Selective Coupling to Receptors*
N-terminal Short Sequences of α Subunits of the G12Family Determine Selective Coupling to Receptors*
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G12 家族 α 亚基的 N 端短序列决定与受体的选择性偶联*
DOI：
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发表时间：
2003
影响因子：
4.8
通讯作者：
M. Negishi
中科院分区：
文献类型：
--
作者：
Y. Yamaguchi;H. Katoh;M. Negishi
异源三聚体G蛋白G12家族的Gα亚基，定义为Gα12和Gα13，具有许多共同的细胞功能，如应力纤维的形成和神经突起的收缩。然而，多种G蛋白偶联受体似乎选择性地与Gα12和Gα13偶联。例如，凝血酶和溶血磷脂酸（LPA）已被证明分别通过Gα12和Gα13诱导应力纤维形成。我们最近发现Gα12和Gα13的活性形式通过其三肽重复结构域与5型丝氨酸/苏氨酸磷酸酶相互作用。我们利用丝氨酸/苏氨酸磷酸酶5型的谷胱甘肽S-转移酶融合的三肽重复结构域与G α 12和G α 13的活性形式强烈相互作用的特性，开发了一种新的测定G α 12和G α 13活性的方法。通过使用该试验，我们确定凝血酶和LPA分别选择性地激活Gα12和Gα13。Gα12和Gα13的氨基酸序列除了N端的短序列外，具有很高的同源性。在此基础上，我们构建了Gα 12 N/13 C和Gα 13 N/12 C嵌合蛋白，其中N端短序列相互替换，并证明凝血酶和LPA分别选择性激活Gα 12 N/13 C和Gα 13 N/12 C。此外，凝血酶和LPA分别通过Gα12和Gα13以Gα12家族N-末端序列依赖性方式刺激RhoA活性。因此，G12家族的N-末端短序列决定了凝血酶和LPA受体与Gα12家族的选择性偶联。
The Gα subunits of the G12family of heterotrimeric G proteins, defined by Gα12 and Gα13, have many cellular functions in common, such as stress fiber formation and neurite retraction. However, a variety of G protein-coupled receptors appear to couple selectively to Gα12 and Gα13. For example, thrombin and lysophosphatidic acid (LPA) have been shown to induce stress fiber formation via Gα12 and Gα13, respectively. We recently showed that active forms of Gα12 and Gα13 interact with Ser/Thr phosphatase type 5 through its tetratricopeptide repeat domain. Here we developed a novel assay to measure the activities of Gα12 and Gα13 by using glutathione S-transferase-fused tetratricopeptide repeat domain of Ser/Thr phosphatase type 5, taking advantage of the property that tetratricopeptide repeat domain strongly interacts with active forms of Gα12 and Gα13. By using this assay, we identified that thrombin and LPA selectively activate Gα12 and Gα13, respectively. Gα12 and Gα13 show a high amino acid sequence homology except for their N-terminal short sequences. Then we generated chimeric G proteins Gα12N/13C and Gα13N/12C, in which the N-terminal short sequences are replaced by each other, and showed that thrombin and LPA selectively activate Gα12N/13C and Gα13N/12C, respectively. Moreover, thrombin and LPA stimulate RhoA activity through Gα12 and Gα13, respectively, in a Gα12 family N-terminal sequence-dependent manner. Thus, N-terminal short sequences of the G12family determine the selective couplings of thrombin and LPA receptors to the Gα12 family.
G α 13 的激活突变体可诱导 NIH 3T3 细胞中的 Egr-1、c-fos 和转化。
影响因子：
8
作者：
VaraPrasad,MV;Shore,SK;Dhanasekaran,N
通讯作者：
Dhanasekaran,N
DOI：
10.1073/pnas.021350998
发表时间：
2001-01-16
影响因子：
11.1
作者：
Meigs, TE;Fields, TA;Casey, PJ
通讯作者：
Casey, PJ