# Structural Studies of PLCepsilon a regulator of cardiac contractility and hypertrophy.

> **NIH NIH R01** · PURDUE UNIVERSITY · 2021 · $378,641

## Abstract

ABSTRACT
Phospholipase C (PLC) enzymes, in particular PLCepsilon, are essential for normal cellular function
in the cardiovascular system. There, they generate second messengers in response to extracellular
signals that increase calcium levels and activate protein kinase C. Misregulation of PLCepsilon is
highly deleterious and can lead to maladaptive changes in cardiac contractility, cell remodeling, and
hypertrophy. Consequently, PLCepsilon is tightly regulated both in its activity and its subcellular
localization. Under basal conditions, the enzyme resides in the cytoplasm and exhibits low activity.
Following the activation of G protein-coupled receptors and/or receptor tyrosine kinases, the enzyme
is allosterically activated and translocated to specific membranes through direct interactions with
small molecular weight GTPases. The small GTPase Rap1A activates and translocates PLCepsilon
to the perinuclear membrane where it stimulates protein kinase cascades involved in cardiac
hypertrophy. However, very little is known about the molecular mechanisms that underlie allosteric
activation of PLCepsilon and its localization by Rap1A. The goal of this proposal is to use an array of
structural, functional, and cell-based studies to provide insights into the molecular mechanisms
underlying the normal and pathological functions of PLCepsilon. In the future, our experiments will aid
in the identification of selective chemical probes for this enzyme and facilitate the development of
novel therapeutic approaches to treat cardiovascular disease, the leading cause of death in the
United States and a rapidly growing problem worldwide.

## Key facts

- **NIH application ID:** 10145758
- **Project number:** 5R01HL141076-04
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** Angeline Marie Lyon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $378,641
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10145758

## Citation

> US National Institutes of Health, RePORTER application 10145758, Structural Studies of PLCepsilon a regulator of cardiac contractility and hypertrophy. (5R01HL141076-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10145758. Licensed CC0.

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