Attempt of G protein-coupled receptor kinase-interacting proteins involved in engulfment of apoptotic cells and role of the receptor kinase in heart disease

2014 Fiscal Year Final Research Report

• Project/Area Number: 25670040
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pharmacology in pharmacy
• Research Institution: Kyushu University
• Principal Investigator: KUROSE HITOSHI 九州大学, 薬学研究科(研究院), 教授 (10183039)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 受容体 / G蛋白質 / 受容体キナーゼ / 貪食 / アポトーシス / 心疾患

Outline of Final Research Achievements

G protein-coupled receptor kinase 6 (GRK6) is a member of GRK family. GRK6 mediates engulfment of apoptotic cells. In this proposal, molecules upstream or downstream of GRK6 were tried to be identified. FRET or BRET probes to detect conformational changes of GRK6 were made. It would facilitate screening of GRK6-interacting proteins. However, the sensitivities of these probes were too low to detect the interaction with putative GRK6-interacting molecules. Using BRET probe, GRK6 was found to be a mediator of TNF-α-stimulated NF-κB activation. Conformation of GRK6 was changed by TNF-α stimulation, and GRK6 bound and phosphorylated IκB-α leading to NF-κB activation. Thus, GRK6 works as a mediator of TNF-α-induced inflammation.

Free Research Field

循環薬理学