# Ceramide Activated Protein Phosphatases

> **NIH NIH R01** · STATE UNIVERSITY NEW YORK STONY BROOK · 2021 · $364,856

## Abstract

Ceramide constitutes a family of closely related molecules that function as
bioeffector lipids with roles in the regulation of stress responses and growth/death of
various human cancer cells. Critical missing elements in our understanding of ceramide
stems from the lack of molecularly-defined targets of action and from defining
compartment-specific functions of ceramides. Studies in our lab supported by this project
have identified ceramide-activated Ser–Thr phosphatases (CAPPs), specifically PP1 and
PP2A as direct targets activated by ceramide in vitro. Studies in cells have also shown
that various ceramide-inducing stimuli (e.g. TNF, UV, lipotoxic agents) induce
dephosphorylation of several substrates in a ceramide-dependent manner. However, not
all stimuli induce all dephosphorylations, presumably due to their activation of distinct
pathways in distinct subcellular compartments. Recent results have provided us a
breakthrough in defining a specific pathway of ceramide generation at the plasma
membrane (PM). Here, we will investigate the hypothesis that ceramide generated at
the PM acutely activates PP1cα that leads to the dephosphorylation of ezrin and other
proteins. This results in a compartment-specific role for ceramide in regulating cell
adhesion and migration. We will address these aims: Aim 1. Define a novel pathway of
ceramide generation at the PM leading to ezrin dephosphorylation though activation of
PP1cα. Here we will investigate the specific hypothesis that PM ceramide regulates a
specific form of dimeric PP1c to mediate ezrin dephosphorylation, independent of raft
formation. Aim 2. Identify specific cellular programs coupled to compartmentalized
ceramide/CAPPs. Here we will investigate the specific hypothesis that PM ceramide,
in contrast to ceramide formed in other compartments, regulates cell adhesion and
migration. Taken together, these approaches should result, for the first time, in clearly
defining a specific, direct, and relevant target for ceramide action (PP1) with a specific
function in mediating the effects of PM ceramide on cell adhesion and migration.

## Key facts

- **NIH application ID:** 10208802
- **Project number:** 5R01CA218678-04
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** YUSUF AWNI HANNUN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $364,856
- **Award type:** 5
- **Project period:** 2018-07-12 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10208802

## Citation

> US National Institutes of Health, RePORTER application 10208802, Ceramide Activated Protein Phosphatases (5R01CA218678-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10208802. Licensed CC0.

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