The association between glycosylphosphatidylinositol-anchored proteins and heterotrimeric G protein alpha subunits in lymphocytes.

The association between glycosylphosphatidylinositol-anchored proteins and heterotrimeric G protein alpha subunits in lymphocytes.
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淋巴细胞中糖基磷脂酰肌醇锚定蛋白与异源三聚体 G 蛋白 α 亚基之间的关联。

DOI:
10.1073/pnas.93.12.6053
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发表时间:
1996
影响因子:
11.1
通讯作者:
Finberg,RW
Finberg,RW
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Solomon,KR;Rudd,CE;Finberg,RW

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糖基磷脂酰肌醇(GPI)锚定蛋白是非跨膜细胞表面蛋白,已被证明是信号转导分子。由于这些蛋白不延伸到细胞质中,这些分子的交联导致细胞内信号转导事件的机制尚不清楚。先前的分析表明,这些蛋白与src家族成员酪氨酸激酶相关;然而,这种相互作用在细胞内信号产生中的作用尚不清楚。在这里,我们发现gpi锚定蛋白与人类和小鼠淋巴细胞中异三聚体GTP结合蛋白(G蛋白)的α亚基相关。当从各种细胞系或新分离的淋巴细胞中免疫沉淀gpi锚定蛋白CD59、CD48和ty -1时,发现它们都与一个41 kda的磷酸化蛋白相关,我们通过使用特定的抗血清鉴定了该蛋白,作为酪氨酸磷酸化的G蛋白α亚基的混合物:少量的Gialpha1,大量的Gialpha2和Gialpha3。用CD59免疫沉淀进行的GTP结合试验表明,该分子具有GTP结合活性。因此,我们已经通过免疫化学和功能标准证明gpi锚定蛋白与G蛋白存在物理关联。这些实验表明,G蛋白在小鼠和人淋巴细胞上表达的gpi锚定分子产生的信号转导中具有潜在的作用。
Glycosylphosphatidylinositol (GPI)-anchored proteins are nonmembrane spanning cell surface proteins that have been demonstrated to be signal transduction molecules. Because these proteins do not extend into the cytoplasm, the mechanism by which cross-linking of these molecules leads to intracellular signal transduction events is obscure. Previous analysis has indicated that these proteins are associated with src family member tyrosine kinases; however, the role this interaction plays in the generation of intracellular signals is not clear. Here we show that GPI-anchored proteins are associated with alpha subunits of heterotrimeric GTP binding proteins (G proteins) in both human and murine lymphocytes. When the GPI-anchored proteins CD59, CD48, and Thy-1 were immunoprecipitated from various cell lines or freshly isolated lymphocytes, all were found to be associated with a 41-kDa phosphoprotein that we have identified, by using specific antisera, as a mixture of tyrosine phosphorylated G protein alpha subunits: a small amount of Gialpha1, and substantial amounts of Gialpha2 and Gialpha3. GTP binding assays performed with immunoprecipitations of CD59 indicated that there was GTP-binding activity associated with this molecule. Thus, we have shown by both immunochemical and functional criteria that GPI-anchored proteins are physically associated with G proteins. These experiments suggest a potential role of G proteins in the transduction of signals generated by GPI-anchored molecules expressed on lymphocytes of both mouse and human.
DOI: 10.1002/eji.1830231110
发表时间: 1993-11-01
影响因子: 5.4
作者:
LUNDJOHANSEN, F;OLWEUS, J;HOREJSI, V
通讯作者: HOREJSI, V