G-PROTEIN DIVERSITY - A DISTINCT CLASS OF ALPHA-SUBUNITS IS PRESENT IN VERTEBRATES AND INVERTEBRATES

G-PROTEIN DIVERSITY - A DISTINCT CLASS OF ALPHA-SUBUNITS IS PRESENT IN VERTEBRATES AND INVERTEBRATES
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DOI:
10.1073/pnas.87.23.9113
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发表时间:
1990-12-01
影响因子:
11.1
通讯作者:
SIMON, MI
SIMON, MI
中科院分区:
综合性期刊1区
文献类型:
--
作者:
STRATHMANN, M;SIMON, MI

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异三聚体鸟嘌呤核苷酸结合蛋白(G 蛋白)是介导细胞对许多激素、神经调节剂和各种其他配体的反应的信号转导途径的组成部分。虽然许多信号传导过程依赖于鸟嘌呤核苷酸,但各种受体、G 蛋白和效应子之间的精确耦合仍然不清楚。我们发现编码 .alpha 的基因家族。异源三聚体 G 蛋白的亚基比之前想象的要大得多。这些新的 α 亚基可以解释 G 蛋白的一些不同活性。我们现在已经获得了编码两种鼠科动物.alpha的cDNA克隆。亚基 G.alpha.q 和 G.alpha.11 88% 相同。它们缺乏通常被百日咳毒素修饰的位点,并且它们的序列与大多数其他 G 蛋白 α 中发现的规范 Gly-Ala-Gly-Glu-Ser (GAGES) 氨基酸序列不同。亚单位。多个长达 7.5 KB 的 mRNA 与 G.alpha.q 特异性探针杂交,并在许多不同组织中以不同水平表达。 G.alpha.11 由单个 4.0-kilobase 消息编码,该消息无处不在。氨基酸序列比较表明G.alpha.q和G.alpha.11代表第三类α。亚单位。在黑腹果蝇中发现了该纲的成员。这个.alpha。亚基 DG.alpha.q 与 G.alpha.q 76% 相同。 Gq 类在脊椎动物和无脊椎动物中的存在表明其在多细胞生物体中的信号转导中发挥着核心作用。我们建议这些 .alpha。亚基可能参与与磷脂酶 C 偶联的百日咳毒素不敏感途径。
Heterotrimereic guanine nucleotide-binding proteins (G proteins) are integral to the signal transduction pathways that mediate the cell''s response to many hormones, neuromodulators, and a variety of other ligands. While many signaling processes are guanine nucleotide dependent, the precise coupling between a variety of receptors, G proteins, and effectors remains obscure. We found that the family of genes that encode the .alpha. subunits of heterotrimeric G proteins is much larger than had previously been supposed. These novel alpha subunits could account for some of the diverse activities attributed to G proteins. We have now obtained cDNA clones encoding two murine .alpha. subunits, G.alpha.q and G.alpha.11, that are 88% identical. They lack the site that is ordinarily modified by pertussis toxin and their sequences vary from the canonical Gly-Ala-Gly-Glu-Ser (GAGES) amino acid sequence found in most other G protein .alpha. subunits. Multiple mRNAs as large as 7.5 kilobases hybridize to G.alpha.q specific probes and are expressed at various levels in many different tissues. G.alpha.11 is encoded by a single 4.0-kilobase message which is expressed ubiquitously. Amino acid sequence comparisons suggest that G.alpha.q and G.alpha.11 represent a third class of .alpha. subunits. A member of this class was found in Drosophila melanogaster. This .alpha. subunit, DG.alpha.q, is 76% identical to G.alpha.q. The presence of the Gq class in both vertebrates and invertebrates points to a role that is central to signal transduction in multicellular organisms. We suggest that these .alpha. subunits may be involved in pertussis toxin-insensitive pathways coupled to phospholipase C.