# AKT phosphorylation of hnRNPA1 modulates T cell fate and function

> **NIH NIH F31** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $45,520

## Abstract

AKT phosphorylation of hnRNPA1 and hnRNPL modulates T cell fate and function
 Regulatory T cells (Treg) play a significant role in maintaining self-tolerance and preventing
autoimmune diseases. We and others have shown that low dose favors Treg and T helper (Th) 2 cell
differentiation, while high Ag dose stimulation activates the PI3K/Akt/mTOR pathway, favoring inflammatory
Th1 and Th17 cell differentiation (Teff). Differences in PI3K/Akt/mTOR signaling not only affect T cell fate but
our research shows that Akt phosphorylation of the RNA-binding protein, (RBP) heterogeneous nuclear
ribonucleoprotein (hnRNP) A1, is dependent on TCR signal strength. RBPs such as hnRNPA1 are emerging
as regulators of RNA processing and stability in immune cells, and the effect of RBP on T cell differentiation is
a growing subject of interest. We have shown hnRNPA1 is required for optimal Treg differentiation by
performing knockdown experiments, and that it is phosphorylated by Akt following low dose stimulation. Our
present research is focused on identifying a role for Akt phosphorylation in hnRNPA1 function. HnRNPA1 is
known to have a single Akt phosphorylation site at S199 and our lab has generated a new mutant mouse
model, hnRNPA1-S199A (mA1). This mutation affects the ability of Akt to phosphorylate hnRNPA1 in all
immune cells. Preliminary data suggest that Treg differentiation induced by low TCR stimulation is impaired in
the T cells from the mutant mouse. Based on these preliminary findings we hypothesize that Akt-mediated
phosphorylation of hnRNPL and/or hnRNPA1 upon low TCR stimulation controls the processing of
RNA transcripts involved in Treg differentiation. The following specific aims are proposed; 1) To determine
how the hnRNPA1-S199A mutation affects T cell fate and function. 2) To determine the impact hnRNPA1 has
on RNA splicing and stability. 3) To identify the AKT phosphorylation site on hnRNPL. 4)To determine how
hnRNPL effects T cell fate and function.

## Key facts

- **NIH application ID:** 9991036
- **Project number:** 1F31AI152320-01
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Tristan Augustus Lenora White
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 1
- **Project period:** 2020-08-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9991036

## Citation

> US National Institutes of Health, RePORTER application 9991036, AKT phosphorylation of hnRNPA1 modulates T cell fate and function (1F31AI152320-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9991036. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*