# Molecular Mechanisms of Cell Signaling

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $748,470

## 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:** 10172922
- **Project number:** 5R35GM122523-05
- **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:** $748,470
- **Award type:** 5
- **Project period:** 2017-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10172922

## Citation

> US National Institutes of Health, RePORTER application 10172922, Molecular Mechanisms of Cell Signaling (5R35GM122523-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10172922. Licensed CC0.

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