GUANINE NUCLEOTIDE BINDING PROTEINS AS RECEPTOR-EFFECTOR COUPLERS

鸟嘌呤核苷酸结合蛋白家族(G蛋白)在 作为受体-效应偶联剂的跨膜信号传递。G蛋白偶联 一系列不同的受体，包括激素的受体， 神经递质、光线、气味和某些生长因子。效应器 G-调节的功能(积极的，在某些情况下是消极的) 蛋白质包括cAMP形成、肌醇磷脂分解、钾和 钙通道和cGMP降解。我们使用了各种不同的 研究表达、分布、调节、结构的技术 和G蛋白的功能。我们的研究突出了 G蛋白家族。使用多肽特异性抗体，我们已经定义了 G蛋白与受体和效应器偶联的特异性。我们有 在阿尔法亚基中产生突变，导致结构性激活， 并将其导入细胞以确定表型对细胞的影响 功能。我们已经确定了G蛋白和G蛋白的突变- 偶联受体是几种人类疾病的基础。这些研究 为理解G蛋白在正常人群中的作用提供了基础 信号转导和阐明G蛋白可能存在的缺陷 作为异常信号转导的基础的结构或功能。

A family of guanine nucleotide binding proteins (G-proteins) functions in transmembrane signalling as receptor-effector couplers. G-proteins couple to a diverse array of receptors including those for hormones, neurotransmitters, light, odorants, and certain growth factors. Effector functions regulated (positively and, in some instances, negatively) by G- proteins include cAMP formation, phosphoinositide breakdown, potassium and calcium channels, and cGMP degradation. We have used a variety of techniques to study the expression, distribution, regulation, structure and function of G-proteins. Our studies highlight the diversity within the G-protein family. Using peptide specific antibodies, we have defined the specificity of G-proteins in coupling to receptors and effectors. We have created mutations in alpha subunits that cause constitutive activation, and transfected these into cells to define phenotypic effects on cellular function. We have identified mutations in G proteins and in G protein- coupled receptors as the basis of several human diseases. These studies provide the basis for understanding the role of G-proteins in normal signal transduction and for elucidating possible defects in G-protein structure or function as the basis for abnormal signal transduction.