# Phosphodiesterases govern nuclear cAMP signaling for gene expression

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2024 · $79,037

## Abstract

Abstract
This application requests an administrative supplement to enhance diversity for the MH134119 grant. The
proposed biochemical and cellular studies are within the scope of the major objectives of the parent grant. The
long-term goal of the candidate is to pursue a career in central nervous system drug development while
mentoring and assisting those from disadvantaged backgrounds. This supplement aims to unveil the source of
subcellular nuclear cAMP after β-adrenergic stimulation, particularly the subcellular adenylyl cyclase (AC)
necessary for nuclear cAMP signal. We aim to test the role of AC5/6, AC9, and soluble AC (sAC) in the β2AR-
induced nuclear cAMP signal. Meanwhile, work from our lab also shows that inhibiting the internalization of the
GRK-pβ2AR attenuates nuclear cAMP. Our lab has shown that the removal of PDE4D5 from the nucleus after β-
adrenergic stimulation is required for GRK-pβ2AR but not PKA-pβ2AR suggesting a distinct but synergistic
control of nuclear cAMP via removal of the PDE4D5 and propagation of cAMP signaling. In this supplement, we
will further uncover the proposed GRK-pβ2AR-arrestin-PDE4D axis via pharmacological and molecular probing
of the role of ACs in nuclear cAMP and gene expression. The proposed study will uncover the mechanisms
behind adrenergic signaling regulation, further supporting the findings in the parent grant. The candidate and the
mentor have worked collaboratively to outline a comprehensive training goal plan that will ensure that the
candidate will receive vital technical training, research experience, and career development to allow him to be
successful with this project and further foster diversity by reducing underrepresentation in the workforce of
scientific research, as outlined in the Research Supplements to Promote Diversity in Health-Related Research
(PA-23-189).

## Key facts

- **NIH application ID:** 11058656
- **Project number:** 3R01MH134119-02S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** YANG Kevin XIANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $79,037
- **Award type:** 3
- **Project period:** 2023-08-15 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11058656

## Citation

> US National Institutes of Health, RePORTER application 11058656, Phosphodiesterases govern nuclear cAMP signaling for gene expression (3R01MH134119-02S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11058656. Licensed CC0.

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