ArticleThe Journal of biological chemistry2015
Hepatocyte growth factor-induced Asef-IQGAP1 complex controls cytoskeletal remodeling and endothelial barrier.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 42 citations in OpenAlex.
- A mechanistic computational model of HGF-VEGF-mediated endothelial cell proliferation and vascular permeability.iScience · 2025Article
- Angiogenesis: Biological Mechanisms and In Vitro Models.Annals of biomedical engineering · 2025Review
- The RhoGEF protein Plekhg5 self-associates via its PH domain to regulate apical cell constriction.Molecular biology of the cell · 2024Article
- Article
- Spatiotemporal regulation of Rho GTPase signaling during endothelial barrier remodeling.Current opinion in physiology · 2023Review
- The IQGAP scaffolds: Critical nodes bridging receptor activation to cellular signaling.The Journal of cell biology · 2023Review
- Article
- Cortactin in Lung Cell Function and Disease.International journal of molecular sciences · 2022Review
- Editorial: Molecular mechanisms of lung endothelial permeability.Frontiers in physiology · 2022Article
- Article
- Microtubules as Major Regulators of Endothelial Function: Implication for Lung Injury.Frontiers in physiology · 2021Review
- Tyrosine phosphorylation of the scaffold protein IQGAP1 in the MET pathway alters function.The Journal of biological chemistry · 2020Article
- Mechanosensitive Rap1 activation promotes barrier function of lung vascular endothelium under cyclic stretch.Molecular biology of the cell · 2019Article
- Incorporation of iloprost in phospholipase-resistant phospholipid scaffold enhances its barrier protective effects on pulmonary endothelium.Scientific reports · 2018Article
- The EPAC-Rap1 pathway prevents and reverses cytokine-induced retinal vascular permeability.The Journal of biological chemistry · 2018Article
- Sphingolipids Signaling in Lamellipodia Formation and Enhancement of Endothelial Barrier Function.Current topics in membranes · 2018Article
- Prostaglandin E receptor-4 receptor mediates endothelial barrier-enhancing and anti-inflammatory effects of oxidized phospholipids.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- Regulation of lung endothelial permeability and inflammatory responses by prostaglandin A2: role of EP4 receptor.Molecular biology of the cell · 2017Article
- Review
- Role of End Binding Protein-1 in endothelial permeability response to barrier-disruptive and barrier-enhancing agonists.Cellular signalling · 2017Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Hepatocyte growth factor (HGF) attenuates agonist-induced endothelial cell (EC) permeability and increases pulmonary endothelial barrier function via Rac-dependent enhancement of the peripheral actin cytoskeleton. However, the precise mechanisms of HGF effects on the peripheral cytoskeleton are not well understood. This study evaluated a role for Rac/Cdc42-specific guanine nucleotide exchange factor Asef and the multifunctional Rac effector, IQGAP1, in the mechanism of HGF-induced EC barrier enhancement. HGF induced Asef and IQGAP1 co-localization at the cell cortical area and stimulated formation of an Asef-IQGAP1 functional protein complex. siRNA-induced knockdown of Asef or IQGAP1 attenuated HGF-induced EC barrier enhancement. Asef knockdown attenuated HGF-induced Rac activation and Rac association with IQGAP1, and it abolished both IQGAP1 accumulation at the cell cortical layer and IQGAP1 interaction with actin cytoskeletal regulators cortactin and Arp3. Asef activation state was essential for Asef interaction with IQGAP1 and protein complex accumulation at the cell periphery. In addition to the previously reported role of the IQGAP1 RasGAP-related domain in the Rac-dependent IQGAP1 activation and interaction with its targets, we show that the IQGAP1 C-terminal domain is essential for HGF-induced IQGAP1/Asef interaction and Asef-Rac-dependent activation leading to IQGAP1 interaction with Arp3 and cortactin as a positive feedback mechanism of IQGAP1 activation. These results demonstrate a novel feedback mechanism of HGF-induced endothelial barrier enhancement via Asef/IQGAP1 interactions, which regulate the level of HGF-induced Rac activation and promote cortical cytoskeletal remodeling via IQGAP1-Arp3/cortactin interactions.
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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.