# P21-activated kinases in cell-cell and cell-matrix adhesion signaling

> **NIH NIH R01** · YALE UNIVERSITY · 2022 · $420,685

## Abstract

P21-activated kinases in cell-cell and cell-matrix adhesion signaling
ABSTRACT
The development and functioning of multicellular organisms, tissue formation, and responses to injury and
infection rely on tightly coordinated adhesion of cells to one another, and of cells to the extracellular matrix.
These processes are mediated in large part through the action of two families of adhesion receptors: the integrins
which are principally responsible for cell-matrix adhesion, and the cadherins which are central to cell-cell
adhesion. Our preliminary data suggest that the type-II p21-activated kinases (PAKs), a group of serine-
threonine kinases, use a range of mechanisms to influence cell-matrix adhesion and cell-cell adhesion. The
ability to regulate both adhesion systems places the PAKs as central players in coordination of cell adhesion
dynamics. This proposal aims to understand the functional, cellular and molecular basis for this regulation. To
address how they control cell-matrix and cell-cell adhesions we propose a combination of structural, biochemical
and cellular approaches. In Aim 1 we test the hypothesis that Direct binding of PAK to cytoplasmic tails of integrin
adhesion receptors regulates matrix adhesion and/or PAK signaling. We will conduct an extensive study
employing structural, biophysical, biochemical and cell biological approaches. This will allow us to
comprehensively understand how integrin adhesion receptors bind PAK serine-threonine kinases, and the
functional consequences of such interactions on cell signaling, adhesion, motility and invasion. In Aim 2 we test
the hypothesis that PAK targeted to cell-cell contacts phosphorylates b-catenin, triggering adhesion turnover and
escape of individual cells from epithelial islands. We will determine the mechanisms by which PAKs drive colony
escape, and the structural basis for PAK regulation of β-catenin. Finally, we will test whether the roles of PAKs
in cell-cell and cell-ECM adhesion are linked. Our proposed work will define how PAKs regulate both integrin-
mediated cell-matrix adhesion, and β-catenin-associated cell-cell adhesion, and therefore will provide new
understanding of interconnections between cell-matrix and cell-cell adhesion via the type-II PAKs.

## Key facts

- **NIH application ID:** 10436342
- **Project number:** 5R01GM138411-03
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Titus Jonathon Boggon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $420,685
- **Award type:** 5
- **Project period:** 2020-09-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10436342

## Citation

> US National Institutes of Health, RePORTER application 10436342, P21-activated kinases in cell-cell and cell-matrix adhesion signaling (5R01GM138411-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10436342. Licensed CC0.

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