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: 5202010
• 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/5202010
• 关键词: G protein; biological signal transduction; gene expression; gene mutation; genetic regulation; human tissue; 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 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.

鸟嘌呤核苷酸结合蛋白（G蛋白）家族在哺乳动物中的功能 作为受体-效应物偶联物的跨膜信号传导。G蛋白偶联 包括激素受体在内的多种受体， 神经递质、光、气味和某些生长因子。执行器 功能调节（积极的，在某些情况下，消极的）由G- 蛋白质包括cAMP形成、磷酸肌醇分解、钾和 钙通道和cGMP降解。我们使用了各种 研究表达、分布、调节、结构的技术 G蛋白的功能。我们的研究强调了 G蛋白家族使用肽特异性抗体，我们已经定义了 G蛋白与受体和效应物偶联的特异性。我们有 在α亚单位中产生突变，导致组成性激活， 并将其转染到细胞中， 功能我们已经发现了G蛋白的突变， 偶联受体作为几种人类疾病的基础。这些研究 为理解G蛋白在正常人中的作用提供了基础。 信号转导和用于阐明G蛋白中可能的缺陷 结构或功能作为异常信号转导的基础。