ArticlePloS one2013
p21-Activated kinase (PAK) regulates cytoskeletal reorganization and directional migration in human neutrophils.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 60 citations in OpenAlex.
- Inwardly rectifying potassium channels promote directional sensing during neutrophil chemotaxis.The Journal of cell biology · 2026Article
- An unexpected tumor-resistant phenotype from floxing PAK1 in a mouse model of colitis associated cancer.Scientific reports · 2025Article
- A role for class I p21-activated kinases in the regulation of the excitability of the actin cytoskeleton.Journal of cell science · 2025Article
- Targeting Neutrophil-Mediated Inflammation: Identification of Pyrazolidinone Carboxamide Derivatives as Potent Selective Inhibitors of Formyl Peptide Receptor 1 (FPR1)-Activated Neutrophils.ACS pharmacology & translational science · 2025Article
- Inwardly rectifying potassium channels regulate membrane potential polarization and direction sensing during neutrophil chemotaxis.bioRxiv : the preprint server for biology · 2025Article
- Fruiting phenology affects the direction of vertical seed dispersal by mammals and birds across mountain ranges.Oecologia · 2025Article
- Regulation of Vascular Injury and Repair by P21-Activated Kinase 1 and P21-Activated Kinase 2: Therapeutic Potential and Challenges.Biomolecules · 2024Review
- KRIT1 in vascular biology and beyond.Bioscience reports · 2024Review
- GTP Signaling Links Metabolism, DNA Repair, and Responses to Genotoxic Stress.Cancer discovery · 2024Article
- Mechanosensitive mTORC2 independently coordinates leading and trailing edge polarity programs during neutrophil migration.Molecular biology of the cell · 2023Article
- KRIT1-mediated regulation of neutrophil adhesion and motility.The FEBS journal · 2023Article
- Random walk and cell morphology dynamics inFrontiers in cell and developmental biology · 2023Article
- Sex-Based Differences in Human Neutrophil Chemorepulsion.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- A chemorepellent inhibits local Ras activation to inhibit pseudopod formation to bias cell movement away from the chemorepellent.Molecular biology of the cell · 2022Article
- Article
- Assessment of the effects of Syk and BTK inhibitors on GPVI-mediated platelet signaling and function.American journal of physiology. Cell physiology · 2021Article
- DOCK7 protects against replication stress by promoting RPA stability on chromatin.Nucleic acids research · 2021Article
- circSFMBT1 promotes pancreatic cancer growth and metastasis via targeting miR-330-5p/PAK1 axis.Cancer gene therapy · 2021Article
- Functional and Therapeutic Relevance of Rho GTPases in Innate Immune Cell Migration and Function during Inflammation: AnMediators of inflammation · 2021Review
- Comparative Proteomic Profiling Identifies Reciprocal Expression of Mitochondrial Proteins Between White and Gray Matter Lesions From Multiple Sclerosis Brains.Frontiers in neurology · 2021Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Neutrophils serve as a first line of defense in innate immunity owing in part to their ability to rapidly migrate towards chemotactic factors derived from invading pathogens. As a migratory function, neutrophil chemotaxis is regulated by the Rho family of small GTPases. However, the mechanisms by which Rho GTPases orchestrate cytoskeletal dynamics in migrating neutrophils remain ill-defined. In this study, we characterized the role of p21-activated kinase (PAK) downstream of Rho GTPases in cytoskeletal remodeling and chemotactic processes of human neutrophils. We found that PAK activation occurred upon stimulation of neutrophils with f-Met-Leu-Phe (fMLP), and PAK accumulated at the actin-rich leading edge of stimulated neutrophils, suggesting a role for PAK in Rac-dependent actin remodeling. Treatment with the pharmacological PAK inhibitor, PF3758309, abrogated the integrity of RhoA-mediated actomyosin contractility and surface adhesion. Moreover, inhibition of PAK activity impaired neutrophil morphological polarization and directional migration under a gradient of fMLP, and was associated with dysregulated Ca(2+) signaling. These results suggest that PAK serves as an important effector of Rho-family GTPases in neutrophil cytoskeletal reorganization, and plays a key role in driving efficient directional migration of human neutrophils.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.