# In Vivo Mechanisms of Integrated G protein Signaling Regulation by RGS Proteins

> **NIH NIH R01** · DREXEL UNIVERSITY · 2020 · $391,250

## Abstract

Title: In Vivo Mechanisms of Integrated G protein Signaling Regulation by RGS Proteins
Project Abstract
G protein signaling is involved in the function of many biological systems including neural, humoral,
autocrine, and paracrine systems that maintain physiological homeostasis. Defects that result in
increased G protein signaling have been implicated in many pathophysiological disorders, most notably
hypertension and heart disease. Therefore, efforts that increase the understanding of G protein
regulation are a major approach to understand disease etiology and develop more effective treatments
for cardiovascular disorders. Regulators of G protein signaling (RGS) regulate G protein signaling by
acting as GTPase-activating proteins (GAPs), accelerating GTP hydrolysis to terminate G protein activity.
Many RGS proteins, including all members of the R4/B subfamily, are highly expressed in organ systems
involved in the control of blood pressure and cardiac function. However, it is not known how the functions
of multiple RGS proteins are integrated or whether they work interdependently to control G protein
signaling in the cardiovascular system to maintain homeostasis. To address these questions, we have
generated mice lacking both RGS2 and 5 (Rgs2/5 dbKO) concurrently. Although these mice are viable,
they develop severe hypertension, have unprovoked cardiac hypertrophy, and the male mice are
extremely sensitive to surgery-induced stress, causing death. The overall goals of the proposal are to
determine the mechanisms that mediate augmented pathological phenotypes and death in Rgs2/5 dbKO
mice, and to determine whether regulation of G protein signaling by RGS2 and 5 are coordinated to
maintain normal cardiovascular physiology. We are poised to address the specific aims in this project by
assembling all the necessary tools and expertise in molecular and cellular biology, echocardiography,
biochemistry, and integrative physiology. Findings from this work will greatly enhance our understanding
of G protein signaling regulation by RGS proteins in the cardiovascular system and elsewhere, thereby
making a broad impact in the field.

## Key facts

- **NIH application ID:** 9850991
- **Project number:** 5R01HL139754-03
- **Recipient organization:** DREXEL UNIVERSITY
- **Principal Investigator:** Patrick Osei-Owusu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $391,250
- **Award type:** 5
- **Project period:** 2018-01-01 → 2020-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9850991

## Citation

> US National Institutes of Health, RePORTER application 9850991, In Vivo Mechanisms of Integrated G protein Signaling Regulation by RGS Proteins (5R01HL139754-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9850991. Licensed CC0.

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