GUANINE NUCLEOTIDE BINDING PROTEINS AS RECEPTOR-EFFECTOR COUPLERS

作为受体-效应器偶联剂的鸟嘌呤核苷酸结合蛋白

• 批准号: 3776957
• 负责人: A SPIEGEL
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3776957
• 关键词: G protein; antibody; gene expression; gene mutation; membrane lipids; posttranslational modifications; protein biosynthesis; protein structure function; receptor coupling; tissue /cell culture; transfection

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 defined distinct post-translational lipid modifications necessary for membrane attachment of G protein alpha and beta/gamma subunits. We have created mutations in alpha subunits that cause constitutive activation, and transfected these into cells to define phenotypic effects on cellular function. 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.

一类鸟嘌呤核苷酸结合蛋白(G蛋白)的功能 在跨膜信号传递中作为受体-效应器偶联剂。G蛋白 连接到一系列不同的受体，包括激素的受体， 神经递质、光气味和某些生长因子。效应器 职能(积极的，在某些情况下是消极的)由 G蛋白包括cAMP形成、肌醇磷脂分解、钾 和钙通道，以及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。我们的研究突出了内部的多样性 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。 我们已经定义了必要的翻译后脂类修饰 用于G蛋白α和β/γ亚基的膜附着。我们 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效应 关于细胞功能。这些研究为理解 G蛋白在正常信号转导和阐明中的作用 可能的G蛋白结构或功能缺陷是 信号转导异常。