ArticleThe Journal of biological chemistry2008
PAK is regulated by PI3K, PIX, CDC42, and PP2Calpha and mediates focal adhesion turnover in the hyperosmotic stress-induced p38 pathway.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
40 citing papers in PubMed, 60 citations in OpenAlex.
- Extracellular stressors change BBSome expression of benign mesothelial and primary pleural mesothelioma cells and affect cell adhesion and migration.Physiological reports · 2026Article
- Nanotopography-Mediated Mechanotransduction Enhances hBMSCs Adhesion on TiOJournal of functional biomaterials · 2026Article
- RABEP1 regulates neutrophil migration via endosomal recycling and actin polymerization.Journal of leukocyte biology · 2026Article
- RABEP1 amplifies front signaling in neutrophil migration.bioRxiv : the preprint server for biology · 2025Article
- Novel kinase regulators of extracellular matrix internalisation identified by high-content screening modulate invasive carcinoma cell migration.PLoS biology · 2024Article
- Neurodevelopmental disorders, like cancer, are connected to impaired chromatin remodelers, PI3K/mTOR, and PAK1-regulated MAPK.Biophysical reviews · 2023Review
- Maternal age affects equine day 8 embryo gene expression both in trophoblast and inner cell mass.BMC genomics · 2022Article
- Group II p21-activated kinase, PAK4, is needed for activation of focal adhesion kinases, MAPK, GSK3, and β-catenin in rat pancreatic acinar cells.American journal of physiology. Gastrointestinal and liver physiology · 2020Article
- Myosin-X is essential to the intercellular spread of HIV-1 Nef through tunneling nanotubes.Journal of cell communication and signaling · 2019Article
- Group I Paks are essential for epithelial- mesenchymal transition in an Apc-driven model of colorectal cancer.Nature communications · 2018Article
- Tissue-Specific Functions ofG3 (Bethesda, Md.) · 2018Article
- The guanine nucleotide exchange factor Arhgef7/βPix promotes axon formation upstream of TC10.Scientific reports · 2018Article
- Overexpression of NELFCD promotes colorectal cancer cells proliferation, migration, and invasion.OncoTargets and therapy · 2018Article
- Loss of ARHGEF6 Causes Hair Cell Stereocilia Deficits and Hearing Loss in Mice.Frontiers in molecular neuroscience · 2018Article
- Omics Approaches to Identify Potential Biomarkers of Inflammatory Diseases in the Focal Adhesion Complex.Genomics, proteomics & bioinformatics · 2017Review
- Group I Paks Promote Skeletal Myoblast Differentiation In Vivo and In Vitro.Molecular and cellular biology · 2017Article
- Down-regulation of p21-activated serine/threonine kinase 1 is involved in loss of mesencephalic dopamine neurons.Molecular brain · 2016Article
- Chronic over-nutrition and dysregulation of GSK3 in diseases.Nutrition & metabolism · 2016Review
- Gastrointestinal hormones/neurotransmitters and growth factors can activate P21 activated kinase 2 in pancreatic acinar cells by novel mechanisms.Biochimica et biophysica acta · 2015Article
- Gα13 Stimulates the Tyrosine Phosphorylation of Ric-8A.Journal of molecular signaling · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fractionation of brain extracts and functional biochemical assays identified PP2Calpha, a serine/threonine phosphatase, as the major biochemical activity inhibiting PAK1. PP2Calpha dephosphorylated PAK1 and p38, both of which were activated upon hyperosmotic shock with the same kinetics. In comparison to growth factors, hyperosmolality was a more potent activator of PAK1. Therefore we characterize the PAK signaling pathway in the hyperosmotic shock response. Endogenous PAKs were recruited to the p38 kinase complex in a phosphorylation-dependent manner. Overexpression of a PAK inhibitory peptide or dominant negative Cdc42 revealed that p38 activation was dependent on PAK and Cdc42 activities. PAK mutants deficient in binding to Cdc42 or PAK-interacting exchange factor were not activated. Using a panel of kinase inhibitors, we identified PI3K acting upstream of PAK, which correlated with PAK repression by pTEN overexpression. RNA interference knockdown of PAK expression reduced stress-induced p38 activation and conversely, PP2Calpha knockdown increased its activation. Hyperosmotic stress-induced PAK translocation away from focal adhesions to the perinuclear compartment and resulted in disassembly of focal adhesions, which are hallmarks of PAK activation. Inhibition of PAK by overexpression of PP2Calpha or the kinase inhibitory domain prevented sorbitol-induced focal adhesion dissolution. Inhibition of MAPK pathways showed that MEK-ERK signaling but not p38 is required for full PAK activation and focal adhesion turnover. We conclude that 1) PAK plays a required role in hyperosmotic signaling through the PI3K/pTEN/Cdc42/PP2Calpha/p38 pathway, and 2) PAK and PP2Calpha modulate the effects of this pathway on focal adhesion dynamics.
Indexed as
Identifiers
What OpenQuestion holds
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.