# Prox1 Phosphorylation in Lymphatic Development and Function

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2020 · $412,500

## Abstract

PROJECT SUMMARY
The homeodomain transcription factor PROX1 is necessary and sufficient for induction and maintenance of
lymphatic endothelial cell identity. It not only plays an essential role in the initial lymphatic reprogramming,
expansion, maturation and maintenance, but also directs formation of luminal and lymphovenous valves.
Although Prox1 has been intensively studied for its function, structure, and regulation, it remains unclear how
such numerous developmental and environmental signals are efficiently incorporated to and regulate Prox1. The
objective of this study is to gain a detailed mechanistic understanding of how lymphangiogenic signals triggered
by growth factors and inflammatory cytokines are transduced to Prox1 protein in the form of phosphorylation,
modulate its properties, and eventually orchestrate lymphatic development and function. We hypothesize that
the RAF-ERK-RSK signal cascade mediates various lymphangiogenic signals and phosphorylates PROX1 at
S79, and that this modification significantly alters the biological properties of Prox1 during lymphatic development
and function. To address these hypotheses, we propose to study of the impact of phospho-S79 to the behaviors
of PROX1, and to elucidate the regulation of lymphangiogenesis by the ERK-RSK2-PROX1 (S79) axis under
the physiological and pathological conditions. Finally, we will generate mutant mouse models that allow a tissue-
specific, conditional replacement of the endogenous wild type Prox1 with its phospho-mutants. Using these
animal models, we will study of the impact of PROX1 S79 phospho-mutation to lymphatic development and
function in health and disease. In summary, the proposed study will define how Prox1 S79 phosphorylation, as
a biomarker of activated lymphatic vessels, regulates physiological and pathological lymphangiogenesis. The
outcome of this study will not only deliver a significant impact on our current understanding of the functional
mode of PROX1 as the master regulator of the lymphatic system, but also offer broader insights into vascular
development and function.

## Key facts

- **NIH application ID:** 9932446
- **Project number:** 5R01DK114645-03
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Young-Kwon Hong
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $412,500
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9932446

## Citation

> US National Institutes of Health, RePORTER application 9932446, Prox1 Phosphorylation in Lymphatic Development and Function (5R01DK114645-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9932446. Licensed CC0.

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