# Optogenetic tools for the dissection of oncogenic signaling mediated by kinases

> **NIH NIH R21** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2020 · $182,886

## Abstract

Aberrant signaling by protein kinases is one of the driving forces of tumorigenesis. Transition from
physiological to oncogenic processes is often triggered by changes in temporal and spatial regulation of
kinases. Dissection of these events is limited by the capabilities of current tools. It remains difficult to
manipulate activity of a specific kinase with precise timing and localization in living cells. To overcome current
limitations we propose to develop a novel broadly applicable optogenetic tool that will allow us to regulate
kinase activity in living cells using light. To control kinase activity in time and space we will engineer a novel
light-sensitive allosteric switch based on fungal photoreceptor Vivid that changes conformation upon
illumination with blue light. Insertion of the engineered switch at a specific site within the catalytic domain of a
kinase will allow us to achieve light-mediated regulation of the activity. This will enable tightly controlled,
reversible and localized regulation of a specific kinase in living cells. To demonstrate broad applicability of this
tool we will use it for regulation of oncogenic protein kinases Src, Abl and PKA. To further expand application
of this strategy we propose to develop light regulated PFKFB3, a structurally different kinase that
phosphorylates fructose 6-phosphate to promote glucose metabolism in cancer cells. The reagents used in this
method will be genetically encoded enabling ready application in many systems. Using light-mediated
regulation of tyrosine kinase Src we will determine its novel role in regulation of signaling pathways that
stimulate glucose metabolism during oncogenic transformation. We will employ light-controlled PFKFB3 to
identify its role in localized regulation of glycolysis in different subcellular compartments of the cell and its effect
on oncogenic morphodynamic changes and cell cycle.

## Key facts

- **NIH application ID:** 9891973
- **Project number:** 5R21CA223915-03
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** ANDREI V KARGINOV
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $182,886
- **Award type:** 5
- **Project period:** 2018-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9891973

## Citation

> US National Institutes of Health, RePORTER application 9891973, Optogenetic tools for the dissection of oncogenic signaling mediated by kinases (5R21CA223915-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9891973. Licensed CC0.

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