RGS4 as a Vascular Brake on Gq Signaling, and How Druggable It Really Is
- RGS4 is a GTPase-activating protein that speeds GTP hydrolysis by Gαq/11 and so switches off GPCR-driven vascular tone, remodeling and inflammatory signaling.
- The review uses the RGS4 crystal structure to lay out its catalytic mechanism and contacts with Gαq/11 and PLCβ, and links the axis to hypertension and other cardiovascular disease.
- It surveys druggable features and the existing docking and MD studies of RGS4 inhibitors.
💡 Points Based on the abstract
RGS proteins are a classic hard target: the interface is a flat protein–protein contact, and most reported inhibitors are covalent or in silico only. The direction of therapy is also unclear, because boosting RGS4 would damp Gq signaling while inhibiting it would amplify it, and the cardiovascular case rests on which way disease tips. I'd ask for genetic human evidence and a validated tool compound before taking this beyond a review.
📄 Paper · Biochemical Pharmacology ↗ The RGS4-Gαq/11 axis in vascular homeostasis: Mechanisms and therapeutic implications