# Molecular Mechanisms of Cell Signaling

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $18,659

## Abstract

Summary/Abstract
 The overall vision of our research is to gain a comprehensive understanding of
the molecular mechanisms driving the function of two major brakes to cell survival signaling,
protein kinas C (PKC) and the PH domain Leucine-rich repeat Protein Phosphatase
(PHLPP, pronounced `flip'). The PKC family has been intensely investigated in the
context of cancer since the discovery in the early 1980s that it is a receptor for the
tumor-promoting phorbol esters. This led to the dogma that activation of PKC by phorbol
esters promotes carcinogen-induced tumorigenesis. Nonetheless, PKC has been an elusive
chemotherapeutic target despite decades of research. We recently established that, contrary
to conventional thinking, PKC is a tumor suppressor, not an oncogene, thus explaining why
30+ years of clinical trials with PKC inhibitors have not only failed but, in some cases,
worsened patient outcome. We are now challenged with understanding the molecular
mechanisms by which PKC isozymes, generally, serve as the brakes to oncogenic signaling.
Our work on PKC led to the discovery of PHLPP, a phosphatase that, by different
mechanisms, also brakes oncogenic signaling but about which considerably less is known
regarding its structure, function, and regulation. We aim to tackle key gaps in our
understanding of the molecular mechanisms that control the amount, activity, and location
of PHLPP in the cell. Uncovering the molecular details of how PKC and PHLPP control cell
signaling will pave the way for novel therapies.

## Key facts

- **NIH application ID:** 10320606
- **Project number:** 3R35GM122523-04S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** ALEXANDRA C. NEWTON
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $18,659
- **Award type:** 3
- **Project period:** 2017-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10320606

## Citation

> US National Institutes of Health, RePORTER application 10320606, Molecular Mechanisms of Cell Signaling (3R35GM122523-04S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10320606. Licensed CC0.

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