ArticleThe Journal of cell biology2010
The PI3K p110alpha isoform regulates endothelial adherens junctions via Pyk2 and Rac1.
Article in The Journal of cell biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 118 citations in OpenAlex.
- Targeting CD4⁺ T cell infiltration: mechanisms and therapeutic insights into CD4⁺ T cell transmigration across the blood-brain barrier in acute ischemic stroke.Fluids and barriers of the CNS · 2026Review
- Anthrax ET activates Rac1 and RTK signaling to induce F-actin reorganization and endothelial permeability.iScience · 2025Article
- Pro-angiogenic potential of the isoxazole derivative ISO-1 via α7-nAChRs activation in human endothelial cells.Biomedical reports · 2025Article
- Deficiency in N-cadherin-Akt3 signaling impairs the blood-brain barrier.Cell reports · 2025Article
- Mesenchymal stem cells and their exosomes: a novel approach to skin regeneration via signaling pathways activation.Journal of molecular histology · 2025Review
- Inhibiting PI3K/Akt-Signaling Pathway Improves Neurobehavior Changes in Anti-NMDAR Encephalitis Mice by Ameliorating Blood-Brain Barrier Disruption and Neuronal Damage.Cellular and molecular neurobiology · 2023Article
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- Dialogue between VE-Cadherin and Sphingosine 1 Phosphate Receptor1 (S1PR1) for Protecting Endothelial Functions.International journal of molecular sciences · 2023Review
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- Elucidating the Ability of CGRP to Modulate Microvascular Events in Mouse Skin.International journal of molecular sciences · 2022Article
- Simulated Microgravity Increases the Permeability of HUVEC Monolayer through Up-Regulation of Rap1GAP and Decreased Rap2 Activation.International journal of molecular sciences · 2022Article
- PI3K Isoforms in Vascular Biology, A Focus on the Vascular System-Immune Response Connection.Current topics in microbiology and immunology · 2022Article
- Targeting PI3K/Akt signal transduction for cancer therapy.Signal transduction and targeted therapy · 2021Review
- VAP-PLGA microspheres (VAP-PLGA) promote adipose-derived stem cells (ADSCs)-induced wound healing in chronic skin ulcers in mice via PI3K/Akt/HIF-1α pathway.Bioengineered · 2021Article
- The up-regulation of miR-21 by gastrodin to promote the angiogenesis ability of human umbilical vein endothelial cells by activating the signaling pathway of PI3K/Akt.Bioengineered · 2021Article
- The role of leukemia inhibitory factor in pathogenesis of pre-eclampsia: molecular and cell signaling approach.Journal of molecular histology · 2021Review
- Gestational Hypoxia and Blood-Brain Barrier Permeability: Early Origins of Cerebrovascular Dysfunction Induced by Epigenetic Mechanisms.Frontiers in physiology · 2021Review
- The Tec Kinase Itk Integrates Naïve T Cell Migration andFrontiers in immunology · 2021Article
- Compensatory increase of VE-cadherin expression through ETS1 regulates endothelial barrier function in response to TNFα.Cellular and molecular life sciences : CMLS · 2020Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Endothelial cell-cell junctions control efflux of small molecules and leukocyte transendothelial migration (TEM) between blood and tissues. Inhibitors of phosphoinositide 3-kinases (PI3Ks) increase endothelial barrier function, but the roles of different PI3K isoforms have not been addressed. In this study, we determine the contribution of each of the four class I PI3K isoforms (p110alpha, -beta, -gamma, and -delta) to endothelial permeability and leukocyte TEM. We find that depletion of p110alpha but not other p110 isoforms decreases TNF-induced endothelial permeability, Tyr phosphorylation of the adherens junction protein vascular endothelial cadherin (VE-cadherin), and leukocyte TEM. p110alpha selectively mediates activation of the Tyr kinase Pyk2 and GTPase Rac1 to regulate barrier function. Additionally, p110alpha mediates the association of VE-cadherin with Pyk2, the Rac guanine nucleotide exchange factor Tiam-1 and the p85 regulatory subunit of PI3K. We propose that p110alpha regulates endothelial barrier function by inducing the formation of a VE-cadherin-associated protein complex that coordinates changes to adherens junctions with the actin cytoskeleton.
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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.