Characterization of the regulatory mechanism controlling Regulator of R‐Protein Signaling‐5 (RGS5) expression

Abstract

We are interested in examining the role of G‐protein coupled receptor (GPCR) signaling with respect to vascular remodeling as a model for cardiovascular disease. The regulator of G‐protein signaling (RGS) protein family primarily functions to control the duration of cellular signals mediated through GPCRs. RGS proteins act as GTPase activating proteins (GAPs) by facilitating the exchange of GDP for GTP upon Gα subunits of the heterotrimeric G‐protein complex, thereby returning the complex to its inactive, yet primed state. RGS5, a member of the RGS‐R4 subfamily of RGS proteins, is the most predominant RGS‐R4 subfamily member expressed in vascular smooth muscle cells (SMCs), and it uniquely identifies arterial SMCs relative to venous SMCs. The putative RGS5 promoter was isolated and characterized by promoter‐luciferase assays in rat aortic SMCs. Chromatin immunoprecipitation (ChIP) assays were performed to confirm the binding of specific transcription factors in vivo. By understanding how RGS5 is regulated, we hope to understand a basic mechanism in determining arterial and venous identity, and to further characterize a key protein in understanding hypertension.