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: 7387462
• 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/7387462
• 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; Urination; 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.

该申请提案要继续，扩展和添加新角度，以调查的作用 血管紧张素II（ANG II）在肌细胞重塑和信号传导机制中。它是基于新发现 表皮接收器和ANG II型1（AT1）受体之间的串扰在细胞外信号反应中 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 包括Janus激酶（JAK2），脯氨酸富酪氨酸激酶（PYK2），含有磷酸酶-2和 - 的SH2 1（SHP-2和SHP-1）蛋白激酶C（尤其是PKC-DELTA）。他们与其他 »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，使这些细胞对他汀类药物的有利作用有反应。 我们提议为信号机制调节的研究添加一个新的角度，以延长AT1的表达 byat2。 根据我们的初步发现，即心脏肥大之前是压力超负荷，这会诱导A 长期增加类型之前，血管紧张素II 2型受体（AT2）表达显着增加 1受体（AT1）表达，我们将评估压力超负荷诱导心脏的假设 肥大和AT1表达受AT2的控制，该AT2激活转录因子前瞻性细胞 锌指蛋白PLZF。这些研究将提供有关心血管机制的重要见解 重塑，将有助于开发特定的治疗疗法和预防方法 应对由于心血管重塑而导致的病态和致命疾病。