| http://purl.uniprot.org/citations/34166557 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/34166557 | http://www.w3.org/2000/01/rdf-schema#comment | "Neovascular age-related macular degeneration (nAMD) is a leading cause of blindness. The pathophysiology involves activation of choroidal endothelial cells (CECs) to transmigrate the retinal pigment epithelial (RPE) monolayer and form choroidal neovascularization (CNV) in the neural retina. The multidomain GTPase binding protein, IQGAP1, binds active Rac1 and sustains activation of CECs, thereby enabling migration associated with vision-threatening CNV. IQGAP1 also binds the GTPase, Rap1, which when activated reduces Rac1 activation in CECs and CNV. In this study, we tested the hypothesis that active Rap1 binding to IQGAP1 is necessary and sufficient to reduce Rac1 activation in CECs, and CNV. We found that pharmacologic activation of Rap1 or adenoviral transduction of constitutively active Rap1a reduced VEGF-mediated Rac1 activation, migration, and tube formation in CECs. Following pharmacologic activation of Rap1, VEGF-mediated Rac1 activation was reduced in CECs transfected with an IQGAP1 construct that increased active Rap1-IQGAP1 binding but not in CECs transfected with an IQGAP1 construct lacking the Rap1 binding domain. Specific knockout of IQGAP1 in endothelial cells reduced laser-induced CNV and Rac1 activation in CNV lesions, but pharmacologic activation of Rap1 did not further reduce CNV compared to littermate controls. Taken together, our findings provide evidence that active Rap1 binding to the IQ domain of IQGAP1 is sufficient to interfere with active Rac1-mediated CEC activation and CNV formation."xsd:string |
| http://purl.uniprot.org/citations/34166557 | http://purl.org/dc/terms/identifier | "doi:10.1096/fj.202100112r"xsd:string |
| http://purl.uniprot.org/citations/34166557 | http://purl.uniprot.org/core/author | "Wang H."xsd:string |
| http://purl.uniprot.org/citations/34166557 | http://purl.uniprot.org/core/author | "Hageman G.S."xsd:string |
| http://purl.uniprot.org/citations/34166557 | http://purl.uniprot.org/core/author | "Hartnett M.E."xsd:string |
| http://purl.uniprot.org/citations/34166557 | http://purl.uniprot.org/core/author | "Sacks D.B."xsd:string |
| http://purl.uniprot.org/citations/34166557 | http://purl.uniprot.org/core/author | "Pappas C."xsd:string |
| http://purl.uniprot.org/citations/34166557 | http://purl.uniprot.org/core/author | "Kunz E."xsd:string |
| http://purl.uniprot.org/citations/34166557 | http://purl.uniprot.org/core/author | "Chaqour B."xsd:string |
| http://purl.uniprot.org/citations/34166557 | http://purl.uniprot.org/core/author | "Ramshekar A."xsd:string |
| http://purl.uniprot.org/citations/34166557 | http://purl.uniprot.org/core/date | "2021"xsd:gYear |
| http://purl.uniprot.org/citations/34166557 | http://purl.uniprot.org/core/name | "FASEB J"xsd:string |
| http://purl.uniprot.org/citations/34166557 | http://purl.uniprot.org/core/pages | "e21642"xsd:string |
| http://purl.uniprot.org/citations/34166557 | http://purl.uniprot.org/core/title | "Active Rap1-mediated inhibition of choroidal neovascularization requires interactions with IQGAP1 in choroidal endothelial cells."xsd:string |
| http://purl.uniprot.org/citations/34166557 | http://purl.uniprot.org/core/volume | "35"xsd:string |
| http://purl.uniprot.org/citations/34166557 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/34166557 |
| http://purl.uniprot.org/citations/34166557 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/34166557 |
| http://purl.uniprot.org/uniprot/#_A0A0U1RPI2-mappedCitation-34166557 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34166557 |
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| http://purl.uniprot.org/uniprot/#_Q05CQ4-mappedCitation-34166557 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34166557 |
| http://purl.uniprot.org/uniprot/#_Q8BPA6-mappedCitation-34166557 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34166557 |
| http://purl.uniprot.org/uniprot/#_Q8CDT3-mappedCitation-34166557 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34166557 |
| http://purl.uniprot.org/uniprot/#_Q8CGH5-mappedCitation-34166557 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34166557 |