ArticlePloS one2013
Rap1 and Rap2 antagonistically control endothelial barrier resistance.
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 34 papers.
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Who cites it
34 citing papers in PubMed, 57 citations in OpenAlex.
- Bioinformatics identification of mitochondrial dynamics-related potential biomarkers in kawasaki disease and prediction of potential regulatory correlations.Frontiers in cardiovascular medicine · 2026Article
- RAP-2-independent roles formicroPublication biology · 2026Article
- Ubiquitylation-dependent Rap2 activation regulates lamellipodia dynamics during cell migration.Journal of cell science · 2025Article
- RASGEF1C methylation for the distinguishment and classification of benign and malignant thyroid tumors.Clinical epigenetics · 2025Article
- MAP4K4 aggravates microvascular anomalies in diabetic retinopathy in a YTHDF2-dependent manner.Diabetologia · 2025Article
- RAP-2 and CNH-MAP4 Kinase MIG-15 confer resistance in bystander epithelium to cell-fate transformation by excess Ras or Notch activity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Rap1 activity and localization is regulated by Rab40/CRL5 facilitated mono-ubiquitylation.microPublication biology · 2025Article
- TNIK: A redox sensor in endothelial cell permeability.Science advances · 2024Article
- RapB Regulates Cell Adhesion and Migration in Dictyostelium, Similar to RapA.Journal of microbiology (Seoul, Korea) · 2024Article
- MAP4K4 regulates forces at cell-cell and cell-matrix adhesions to promote collective cell migration.Life science alliance · 2023Article
- Abrogation of MAP4K4 protein function causes congenital anomalies in humans and zebrafish.Science advances · 2023Article
- Review
- Integrin-Dependent Cell-Matrix Adhesion in Endothelial Health and Disease.Circulation research · 2023Review
- Editorial: Diverse roles of MAP4K4 in MAP kinase signaling and its implication for cancer therapeutics.Frontiers in oncology · 2023Article
- ArhGEF12 activates Rap1A and not RhoA in human dermal microvascular endothelial cells to reduce tumor necrosis factor-induced leak.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Simulated Microgravity Increases the Permeability of HUVEC Monolayer through Up-Regulation of Rap1GAP and Decreased Rap2 Activation.International journal of molecular sciences · 2022Article
- GPCR-mediated YAP/TAZ inactivation in fibroblasts via EPAC1/2, RAP2C, and MAP4K7.Journal of cellular physiology · 2021Article
- MAP4K4 expression in cardiomyocytes: multiple isoforms, multiple phosphorylations and interactions with striatins.The Biochemical journal · 2021Article
- Role of Adenosine and Purinergic Receptors in Myocardial Infarction: Focus on Different Signal Transduction Pathways.Biomedicines · 2021Review
- MAP4K4 induces early blood-brain barrier damage in a murine subarachnoid hemorrhage model.Neural regeneration research · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rap1 and Rap2 are closely related proteins of the Ras family of small G-proteins. Rap1 is well known to regulate cell-cell adhesion. Here, we have analysed the effect of Rap-mediated signalling on endothelial permeability using electrical impedance measurements of HUVEC monolayers and subsequent determination of the barrier resistance, which is a measure for the ease with which ions can pass cell junctions. In line with its well-established effect on cell-cell junctions, depletion of Rap1 decreases, whereas activation of Rap1 increases barrier resistance. Despite its high sequence homology with Rap1, depletion of Rap2 has an opposite, enhancing, effect on barrier resistance. This effect can be mimicked by depletion of the Rap2 specific activator RasGEF1C and the Rap2 effector MAP4K4, establishing Rap2 signalling as an independent pathway controlling barrier resistance. As simultaneous depletion or activation of both Rap1 and Rap2 results in a barrier resistance comparable to control cells, Rap1 and Rap2 control barrier resistance in a reciprocal manner. This Rap1-antagonizing effect of Rap2 is established independent of junctional actin formation. These data establish that endothelial barrier resistance is determined by the combined antagonistic actions of Rap1 and Rap2.
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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.