The search for the novel bioactive peptide that activates G protein-coupled receptor coupled to G12/13 proteins

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461400
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Endocrinology
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: MORI Miwa 国立研究開発法人国立循環器病研究センター, 研究所, 特任研究員 (50363148)
• Co-Investigator(Kenkyū-buntansha): MORI Kenji 国立研究開発法人国立循環器病研究センター, 研究所, 室長 (00416223)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 内分泌 / 生理活性ペプチド / 受容体

Outline of Final Research Achievements

There are some G protein-coupled receptors (GPCR) coupled to G12/13 protein, such as endothelin B receptor and angiotensin 1 receptor. However, the search of novel bioactive peptide based on the activation of G12/13 signaling pathway has not been successful so far, because it has been difficult to easily detect such activation.
The SRF-RE luciferase reporter is activated in response to activation of GPCR coupled to G12/13 protein. In this study, it was demonstrated that this reporter gene assay is suitable to search novel bioactive peptide that activates G12/13 signaling pathway through GPCR. This assay was detected that endothelin-1 induced dose-dependent, robust increase in SRF-RE reporter activity in HEK293 cells expressing endothelin B receptor with EC50 of 0.3nM, indicating that the sensitivity of this assay is sufficient for searching the novel bioactive peptide. Therefore, we are searching the novel bioactive peptide as endogenous ligand for orphan GPCRs by using this assay.

Free Research Field

生化学、ペプチド化学