# G Protein-Coupled Receptor Regulation in Airway Myocytes

> **NIH NIH R01** · THOMAS JEFFERSON UNIVERSITY · 2021 · $557,773

## Abstract

Project Description
 It is now appreciated the cell often compartmentalizes signaling, presumably as a means of expanding its
diversity of control over how it functions. Importantly, this complexity in signaling expands the number of
druggable targets, and the ability to modulate specific cell functions linked to compartmentalized signaling. Our
recent data suggest that different members of the GPCR subfamily of Gs-coupled receptors exhibit distinct
compartmentalized signaling in ASM, affecting both the quantitative and qualitative nature of the signaling,
which may explain the receptor’s differential capacity to regulate ASM functions. Studies in this proposal will
therefore test the hypothesis that distinct complements of signaling effectors and regulators serve to
compartmentalize signaling in ASM cells, resulting in differential ability of β2AR and prostaglandin E (EP)
receptors to regulate ASM contraction. This hypothesis will be tested in 3 Specific Aims. Aim 1 will employ
cutting edge imaging, biochemical, proteomic, and molecular biology approaches to establish that β2AR, EP2,
and EP4 receptor signaling occurs in different cellular regions to produce quantitatively and qualitatively
different outcomes. In Aim 2 we will target multiple putative regulators of compartmentalized signaling to
establish the mechanistic basis for the distinct signaling by each of the receptors. In Aim 3 we will similarly
target mechanisms of receptor compartmentalization in order to link the compartmentalized signaling of β2AR,
EP2 and EP4 receptors to differential regulation of ASM contraction. The basic science goal of these studies is
to delineate mechanisms by which the cell compartmentalizes signals for different Gs-coupled receptors in a
relevant primary cell type, and link this regulation to changes in cell function. The translational goal is to identify
new therapeutic targets and strategies, enabling a greater number of more selective and efficacious
approaches to managing the asthma phenotype.

## Key facts

- **NIH application ID:** 10074583
- **Project number:** 5R01HL058506-23
- **Recipient organization:** THOMAS JEFFERSON UNIVERSITY
- **Principal Investigator:** RAYMOND B. PENN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $557,773
- **Award type:** 5
- **Project period:** 1997-08-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10074583

## Citation

> US National Institutes of Health, RePORTER application 10074583, G Protein-Coupled Receptor Regulation in Airway Myocytes (5R01HL058506-23). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10074583. Licensed CC0.

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