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Title: The Cdc42 effector kinase PAK4 localizes to cell-cell junctions and contributes to establishing cell polarity
Authors: Selamat W.
Tay P.-L.F.
Baskaran Y.
Manser E. 
Keywords: beta catenin
p21 activated kinase 4
protein Cdc42
protein serine threonine kinase inhibitor
beta catenin
CTNNB1 protein, human
p21 activated kinase
PAK4 protein, human
PF 3758309
protein Cdc42
protein kinase inhibitor
pyrazole derivative
pyrrole derivative
animal cell
cell junction
cell migration
cell polarity
complex formation
focal adhesion
human cell
MCF 7 cell line
monolayer culture
protein assembly
protein depletion
protein localization
protein phosphorylation
U2OS cell line
antagonists and inhibitors
cell junction
drug effects
gene silencing
MCF-7 cell line
tumor cell line
beta Catenin
cdc42 GTP-Binding Protein
Cell Line, Tumor
Cell Polarity
Gene Knockdown Techniques
Intercellular Junctions
MCF-7 Cells
p21-Activated Kinases
Protein Kinase Inhibitors
Issue Date: 2015
Citation: Selamat W., Tay P.-L.F., Baskaran Y., Manser E. (2015). The Cdc42 effector kinase PAK4 localizes to cell-cell junctions and contributes to establishing cell polarity. PLoS ONE 10 (6) : e0129634. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: The serine/threonine kinase PAK4 is a Cdc42 effector whose role is not well understood; overexpression of PAK4 has been associated with some cancers, and there are reports that correlate kinase level with increased cell migration in vitro. Here we report that PAK4 is primarily associated with cell-cell junctions in all the cell lines we tested, and fails to accumulate at focal adhesions or at the leading edge of migrating cells. In U2OS osteosarcoma and MCF-7 breast cancer cell lines, PAK4 depletion did not affect collective cell migration, but affected cell polarization. By contrast, Cdc42 depletion (as reported by many studies) caused a strong defect in junctional assembly in multiple cells lines. We also report that the depletion of PAK4 protein or treatment of cells with the PAK4 inhibitor PF-3758309 can lead to defects in centrosome reorientation (polarization) after cell monolayer wounding. These experiments are consistent with PAK4 forming part of a conserved cell-cell junctional polarity Cdc42 complex. We also confirm ?-catenin as a target for PAK4 in these cells. Treatment of cells with PF-3758309 caused inhibition of ?-catenin Ser-675 phosphorylation, which is located predominantly at cell-cell junctions. © 2015 Selamat et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Source Title: PLoS ONE
ISSN: 19326203
DOI: 10.1371/journal.pone.0129634
Rights: Attribution 4.0 International
Appears in Collections:Staff Publications

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