ArticleThe Journal of biological chemistry2013
Pak2 kinase restrains mast cell FcεRI receptor signaling through modulation of Rho protein guanine nucleotide exchange factor (GEF) activity.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- CD20 tails interact with the 14-3-3/GEF-H1 complex and microtubule network upon PKCδ phosphorylation.The EMBO journal · 2026Article
- Review
- Machine Learning Prediction of Treatment Response to Inhaled Corticosteroids in Asthma.Journal of personalized medicine · 2024Article
- Article
- Pak2-mediated phosphorylation promotes RORγt ubiquitination and inhibits colonic inflammation.Cell reports · 2022Article
- PAK-dependent regulation of actin dynamics in breast cancer cells.The international journal of biochemistry & cell biology · 2022Review
- Differential role for PAK1 and PAK4 during the invadopodia lifecycle.Small GTPases · 2019Article
- Unfractionated heparin ameliorates pulmonary microvascular endothelial barrier dysfunction via microtubule stabilization in acute lung injury.Respiratory research · 2018Article
- Group I Paks are essential for epithelial- mesenchymal transition in an Apc-driven model of colorectal cancer.Nature communications · 2018Article
- Modulation of store-operated calcium entry and nascent adhesion by p21-activated kinase 1.Experimental & molecular medicine · 2018Article
- p21-Activated Kinase 2 Regulates Endothelial Development and Function through the Bmk1/Erk5 Pathway.Molecular and cellular biology · 2015Article
- Pak2 restrains endomitosis during megakaryopoiesis and alters cytoskeleton organization.Blood · 2015Article
- Pak2 regulates hematopoietic progenitor cell proliferation, survival, and differentiation.Stem cells (Dayton, Ohio) · 2015Article
- Article
- Dynamic association of the PI3P-interacting Mon1-Ccz1 GEF with vacuoles is controlled through its phosphorylation by the type 1 casein kinase Yck3.Molecular biology of the cell · 2014Article
- Control of vascular permeability by atrial natriuretic peptide via a GEF-H1-dependent mechanism.The Journal of biological chemistry · 2014Article
- Group I PAK inhibitor IPA-3 induces cell death and affects cell adhesivity to fibronectin in human hematopoietic cells.PloS one · 2014Article
- Potential compensation among group I PAK members in hindlimb ischemia and wound healing.PloS one · 2014Article
- PAK signalling during the development and progression of cancer.Nature reviews. Cancer · 2014Review
- Role of p21-activated kinases in cardiovascular development and function.Cellular and molecular life sciences : CMLS · 2013Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
p21-activated kinase-1 (Pak1) is a serine/threonine kinase that plays a key role in mediating antigen-stimulated extracellular calcium influx and degranulation in mast cells. Another isoform in this kinase family, Pak2, is expressed at very high levels in mast cells, but its function is unknown. Here we show that Pak2 loss in murine bone marrow-derived mast cells, unlike loss of Pak1, induces increased antigen-mediated adhesion, degranulation, and cytokine secretion without changes to extracellular calcium influx. This phenotype is associated with an increase in RhoA-GTPase signaling activity to downstream effectors, including myosin light chain and p38(MAPK), and is reversed upon treatment with a Rho-specific inhibitor. Pak2, but not Pak1, negatively regulates RhoA via phosphorylation of the guanine nucleotide exchange factor GEF-H1 at an inhibitory site, leading to increased GEF-H1 microtubule binding and loss of RhoA stimulation. These data suggest that Pak2 plays a unique inhibitory role in mast cell degranulation by down-regulating RhoA via GEF-H1.
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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.