Hildebrandt J D
Department of Cell and Molecular Pharmacology, Medical University of South Carolina, Charleston 29425-2251, U.S.A.
Biochem Pharmacol. 1997 Aug 1;54(3):325-39. doi: 10.1016/s0006-2952(97)00269-4.
The heterotrimeric G proteins are extensively involved in the regulation of cells by extracellular signals. The receptors that control them are often the targets of drugs. There are many isoforms of each of the three subunits that make up these proteins. Thus far, genes for at least sixteen alpha subunits, five beta subunits, and eleven gamma subunits have been identified. In addition, some of these proteins have splice variants or are differentially modified. Based upon what is already known, there are well over a thousand possible G protein heterotrimer combinations. The role of subunit diversity in heterotrimer formation and its effect on signaling by G proteins are still not well understood. However, many current lines of research are leading toward an understanding of these roles. The functional significance of subunit heterogeneity is related to the mechanisms used by G proteins to transmit and integrate the many signals coming into cells through this system. Described here are the basic mechanisms by which G proteins integrate cellular responses, the possible role of subunit heterogeneity in these mechanisms, and the evidence for and against their physiological significance. Recent studies suggest the likely possibility that subunit heterogeneity plays an important role in signaling by G proteins. This role has the potential to extend substantially the flexibility of G proteins in mediating cellular responses to extracellular signals. However, the details of this are yet to be worked out, and they are the subject of many different avenues of research.
异源三聚体G蛋白广泛参与细胞外信号对细胞的调控。控制它们的受体常常是药物的作用靶点。组成这些蛋白的三个亚基中的每一个都有许多亚型。到目前为止，至少已鉴定出16种α亚基、5种β亚基和11种γ亚基的基因。此外，这些蛋白中的一些有剪接变体或存在差异修饰。基于已知信息，可能的G蛋白异源三聚体组合超过一千种。亚基多样性在异源三聚体形成中的作用及其对G蛋白信号传导的影响仍未完全清楚。然而，目前许多研究方向正朝着了解这些作用发展。亚基异质性的功能意义与G蛋白通过该系统传递和整合进入细胞的众多信号所采用的机制有关。这里描述的是G蛋白整合细胞反应的基本机制、亚基异质性在这些机制中的可能作用，以及支持和反对其生理意义的证据。最近的研究表明亚基异质性在G蛋白信号传导中可能发挥重要作用。这一作用有可能极大地扩展G蛋白在介导细胞对细胞外信号反应中的灵活性。然而，其中的细节仍有待阐明，它们是许多不同研究途径的主题。
