Angiotensin Receptor AT1 in Cardiovascular Cell Control.

心血管细胞控制中的血管紧张素受体 AT1。

• 批准号: 7591094
• 负责人: TADASHI INAGAMI
• 金额: $ 37.26万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-10 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7591094
• 关键词: 70-kDa Ribosomal Protein S6 Kinases; Address; Angiotensin II; Antihypertensive Agents; Atherosclerosis; Biochemical; Biological; Blood Vessels; Calcium; Cardiovascular Diseases; Cardiovascular system; Cells; Disease; Environment; Enzyme Inhibitor Drugs; Enzyme Inhibitors; Enzymes; Epidermal Growth Factor Receptor; FOS gene; G-Protein-Coupled Receptors; Generations; Goals; Growth; Heart failure; Homeostasis; Hyperplasia; Hypertension; Hypertrophy; JAK2 gene; Kidney; Knowledge; Ligands; Link; MAPK14 gene; MAPK8 gene; Mediating; Metalloproteases; Mitogen-Activated Protein Kinases; Molecular; PTK2B gene; PTPN11 gene; Peptides; Phosphoric Monoester Hydrolases; Phosphotransferases; Play; Protein Synthesis Induction; Protein Tyrosine Kinase; Protein Tyrosine Phosphatase; Proto-Oncogene Proteins c-akt; Rattus; Reactive Oxygen Species; Receptor Protein-Tyrosine Kinases; Receptor, Angiotensin, Type 1; Regulation; Renin-Angiotensin System; Reporting; Research; Role; Signal Transduction; Smooth Muscle Myocytes; Tissues; Transactivation; Vascular remodeling; experience; growth promoting activity; protective effect; receptor; receptor function; therapeutic target

This application proposes to continue, extend and add new angles to the investigation of the role of angiotensin II (Ang II) in myocyte remodeling and signaling mechanisms for it. It is based on new findings of cross-talk between epidermal receptor and the Ang II type 1 (AT1) receptor in extracellular signal-response kinase (ERK), as well as involvement of several non-receptor tyrosine kinases and tyrosine phosphatases which include Janus kinase (JAK2), proline rich tyrosine kinase (PYK2), SH2 containing phosphatase-2 and - 1 (SHP-2 and SHP-1) protein kinases C (particularly PKC-delta). They form a large complex with other ¿caffold proteins Gab1, and small G-protein Rap1, and they are responsible for activation of cJun NH2- kinase (JNK), cellular migration and make these cells responsive to favorable action of statins. We propose to add a new angle to studies on signaling mechanism regulating prolonged expressionof AT1 byAT2. Based on our preliminary finding that cardiac hypertrophy is preceded by pressure overload, which induces a marked increase in the angiotensin II type 2 receptor (AT2) expression before long term increase in the type 1 receptor (AT1) expression, we will evaluate the hypothesis that pressure overload induced cardiac hypertrophy and AT1 expression is controlled by AT2, which activate the transcription factor promyelocytic zinc finger protein PLZF. These studies will provide important insights into the mechanism of cardiovascular remodeling and will be useful for developing specific therapeutic remedies and preventative approaches to cope with morbid and mortal diseases due to cardiovascular remodeling.

本申请建议继续、扩展和增加新的角度来研究 血管紧张素II（Ang II）在心肌细胞重塑及其信号传导机制中的作用是基于它的新发现。 细胞外信号反应中表皮受体与 Ang II 1 型 (AT1) 受体之间的串扰 激酶 (ERK)，以及几种非受体酪氨酸激酶和酪氨酸磷酸酶的参与 其中包括 Janus 激酶 (JAK2)、富含脯氨酸的酪氨酸激酶 (PYK2)、含有磷酸酶 2 的 SH2 和 - 1（SHP-2 和 SHP-1）蛋白激酶 C（特别是 PKC-delta）它们与其他蛋白激酶形成大型复合物。 ¿ caffold 蛋白 Gab1 和小 G 蛋白 Rap1，它们负责激活 cJun NH2- 激酶（JNK）、细胞迁移并使这些细胞对他汀类药物的有利作用做出反应。 我们建议为调控AT1延长表达的信号机制研究增加一个新的角度 通过AT2。 根据我们的初步发现，心脏肥大先于压力超负荷，从而导致心脏肥大 血管紧张素 II 2 型受体 (AT2) 表达显着增加，然后该类型长期增加 1 受体 (AT1) 表达，我们将评估压力超负荷诱发心脏的假设 肥大和 AT1 表达受 AT2 控制，AT2 激活转录因子早幼粒细胞 这些研究将为心血管机制提供重要的见解。 重塑，并将有助于开发特定的治疗方法和预防方法 应对因心血管重塑引起的病态和致命疾病。