Interaction of RSK2 with 5-HT2A receptor

RSK2 与 5-HT2A 受体的相互作用

• 批准号: 6585422
• 负责人: DOUGLAS J SHEFFLER
• 金额: $ 3.28万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-12-01 至 2004-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6585422
• 关键词: binding sites; biological signal transduction; cell line; confocal scanning microscopy; disease /disorder etiology; enzyme activity; genetic disorder; human genetic material tag; immunocytochemistry; immunoprecipitation; mental retardation; mitogen activated protein kinase; predoctoral investigator; protein kinase; protein protein interaction; psychosis; receptor binding; serotonin receptor; site directed mutagenesis; skeletal disorder; syndrome; yeast two hybrid system

DESCRIPTION (provided by applicant): The goal of the proposed research is to verify the interaction of RSK2 with the third intracellular loop of the 5-HT2A receptor that was identified in a yeast-2-hybrid screen. Once this interaction has been established, its functional significance will be determined. Our central hypothesis is that RSK2 interacts with the 5-HT2A receptor, indicating a role in signal transduction. It is likely that this interaction plays a role in the ligand-dependent activation of the MAP Kinase cascade by the 5-HT2A receptor. Inactivating mutations in the RSK2 gene are responsible for the human Coffin-Lowry syndrome. This syndrome is characterized by severe non-specific mental retardation, psychosis, and progressive skeletal deformations. The psychosis that is present in Coffin-Lowry syndrome may prove to be attributed to a disfunction of 5-HT2A signaling. To test this central idea we propose to verify the interaction of the 5-HT2A receptor's third intracellular loop and RSK2 via coimmunoprecipitation studies and through confocal microscopy studies. The binding site of RSK2 to the 5-HT2A receptor will be defined via site-directed mutageneis studies in conjunction with 2-hybrid analysis. The functional role of the interaction between RSK2 and the 5-HT2A receptor will be defined.

描述（由申请人提供）：拟议研究的目标是验证 RSK2 与在酵母 2 杂交筛选中鉴定出的 5-HT2A 受体的第三个细胞内环的相互作用。一旦建立了这种相互作用，其功能意义就确定了。我们的中心假设是 RSK2 与 5-HT2A 受体相互作用，表明在信号转导中发挥作用。这种相互作用很可能在 5-HT2A 受体对 MAP 激酶级联的配体依赖性激活中发挥作用。 RSK2 基因的失活突变是导致人类 Coffin-Lowry 综合征的原因。该综合征的特点是严重的非特异性智力低下、精神病和进行性骨骼变形。 Coffin-Lowry 综合征中出现的精神病可能是由于 5-HT2A 信号传导功能障碍所致。为了测试这一中心思想，我们建议通过免疫共沉淀研究和共聚焦显微镜研究来验证 5-HT2A 受体的第三个细胞内环与 RSK2 的相互作用。 RSK2 与 5-HT2A 受体的结合位点将通过定点诱变研究结合 2 杂交分析来确定。 RSK2 和 5-HT2A 受体之间相互作用的功能作用将被定义。