# mTORC2 signaling in metabolism and cell fate

> **NIH NIH R01** · RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL · 2021 · $326,040

## Abstract

ABSTRACT
Cell fate is influenced by the interplay of signals from the extracellular and intracellular
environment. Studies over the years have revealed how the quality and quantity of
signals triggered extracellular growth receptors mobilize intracellular signaling molecules
leading to gene expression changes that dictate cell responses or fate. How such
signals affect nutrient metabolism and how nutrient metabolites in turn control
intracellular signaling, gene expression and ultimately cell fate remains poorly
understood. A central signaling molecule that responds to nutrients and controls
metabolism is mTOR. mTOR is an atypical Ser/Thr protein kinase that forms two protein
complexes, mTORC1 and mTORC2. Numerous studies have focused on mTORC1,
which is inhibited by the natural compound, rapamycin. mTORC1 is active in the
presence of amino acids and promotes anabolic metabolism. In contrast to mTORC1,
the regulation and functions of mTORC2 are poorly understood. In higher eukaryotes,
mTORC2 is activated by growth factors such as insulin. Our project will elucidate how
mTORC2 is involved in determining cell fate via its role in metabolic reprogramming
during nutrient fluctuations. We will focus on how mTORC2 regulates the hexosamine
biosynthetic pathway to control early thymocyte development. Our findings have
implications for understanding how metabolism impacts cellular differentiation
particularly in early T cell development. A deeper understanding of the regulation and
functions of the mTOR complexes is needed for more effective therapeutic strategies
against metabolic aberrations that occur during aging and diseases such as
autoimmunity, diabetes and cancer.

## Key facts

- **NIH application ID:** 10133100
- **Project number:** 5R01GM137493-02
- **Recipient organization:** RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL
- **Principal Investigator:** Estela Jacinto
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $326,040
- **Award type:** 5
- **Project period:** 2020-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10133100

## Citation

> US National Institutes of Health, RePORTER application 10133100, mTORC2 signaling in metabolism and cell fate (5R01GM137493-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10133100. Licensed CC0.

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