# Out of the shadows: Illuminating mammalian histidine phosphorylation

> **NIH NIH R35** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2024 · $440,000

## Abstract

Project Summary
Protein histidine phosphorylation plays an important role in several key signaling pathways in
mammals but is very poorly understood. The main reasons for this dearth of information about
histidine phosphorylation are the relative instability of pHis as compared to pSer, pThr, and pTyr
and a complete lack of chemical tools available to monitor and modulate the enzymes involved
in histidine phosphorylation and dephosphorylation. The Barrios laboratory is working to develop
fluorogenic assays that can be applied to monitoring cellular histidine phosphatase and histidine
kinase activity and to develop the first inhibitors of mammalian histidine phosphatase and
histidine kinase activity. We will investigate the structural and sequence contexts that facilitate
histidine phosphorylation and stabilize the resulting pHis residue and characterize the effects
that histidine phosphorylation has on protein structure and function, including enzymatic activity
and ability to bind metal ions. The tools, fundamental insights, and specific examples developed
in this work will facilitate future research into the biological roles of the histidine phosphatases
and kinases and are expected to revolutionize the field. The ultimate goal of the work is to
elucidate the roles that histidine kinases and phosphatases play in cellular signaling, health, and
disease and to identify promising therapeutic targets and lead compounds that act on histidine
phosphorylation pathways.

## Key facts

- **NIH application ID:** 10832386
- **Project number:** 1R35GM153175-01
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** AMY M BARRIOS
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $440,000
- **Award type:** 1
- **Project period:** 2024-04-01 → 2029-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10832386

## Citation

> US National Institutes of Health, RePORTER application 10832386, Out of the shadows: Illuminating mammalian histidine phosphorylation (1R35GM153175-01). Retrieved via AI Analytics 2026-05-30 from https://api.ai-analytics.org/grant/nih/10832386. Licensed CC0.

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