G protein-coupled receptor:its crosstalk, diseases, and regulation

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461382
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Endocrinology
• Research Institution: St. Marianna University School of Medicine (2014-2015); The University of Tokyo (2013)
• Principal Investigator: Iiri Taroh 聖マリアンナ医科大学, 医学部, 教授 (90313022)
• Co-Investigator(Kenkyū-buntansha): MAKITA NORIKO 東京大学, 医学部付属病院, 講師 (60353455)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: Gタンパク質共役受容体 / GPCR / NO / nitrosylation / 臓器障害と保護 / メタボリックシンドローム / シグナルクロストーク

Outline of Final Research Achievements

We have investigated the molecular mechanism of the crosstalk between Gs-coupled receptors and Gq/G13-coupled receptors, focusing on RhoA/RhoGDI function, and have found that RhoGDI phosphorylation by A-kinase serves as the specific inhibitory mechanism of Gq/G11-coupled receptor signaling. We have also investigated the molecular mechanism of desensitization of Gs-coupled receptor, focusing on GPCR kinase 2 (GRK2), and shown that our novel chemicals that induce nitrosylation of GRK2 inhibit GRK2 function and desensitization of β-adrenergic receptor, thus clarifying the signal crosstalk between NO and GPCRs. We have also quantitatively shown that angiotensin receptor blockers (ARBs) show dual actions, i.e., inverse agonist activity to AT1 receptor and anti-inflammation activity against adipocytes/macrophages.

Free Research Field

内分泌学、分子生物学、内科学、薬理学、GPCRシグナル制御と疾患