{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T21:30:39Z","timestamp":1755034239253,"version":"3.38.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2020,10,1]],"date-time":"2020-10-01T00:00:00Z","timestamp":1601510400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Connie Frank and Evan Thompson Program for Collaborative Restorative Transplantation","award":["RO1 AI135201","U19 AI128913","P01AI120944","U01 AI-124319"],"award-info":[{"award-number":["RO1 AI135201","U19 AI128913","P01AI120944","U01 AI-124319"]}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01 DK100405","P30 DK041301","P01CA236585","1I01BX003801"],"award-info":[{"award-number":["R01 DK100405","P30 DK041301","P01CA236585","1I01BX003801"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Ab cross-linking of HLA class I (HLA I) molecules on the surface of endothelial cells (EC) triggers proliferative and prosurvival intracellular signaling, which is implicated in the process of chronic allograft rejection, also known as transplant vasculopathy. Despite the importance of Ab-mediated rejection in transplantation, the mechanisms involved remain incompletely understood. In this study, we examined the regulation of yes-associated protein (YAP) localization, phosphorylation, and transcriptional activity in human ECs challenged with Abs that bind HLA I. In unstimulated ECs, YAP localized mainly in the cytoplasm. Stimulation of these cells with Ab W6\/32 induced marked translocation of YAP to the nucleus. The nuclear import of YAP was associated with a rapid decrease in YAP phosphorylation at Ser127 and Ser397, sites targeted by LATS1\/2 and with the expression of YAP-regulated genes, including connective tissue growth factor (CTGF), and cysteine-rich angiogenic inducer 61 (CYR61). Transfection of small interfering RNAs targeting YAP\/TAZ blocked the migration of ECs stimulated by ligation of HLA I, indicating that YAP mediates the increase in EC migration induced by HLA I ligation. Treatment of intact ECs with Src family inhibitors induced cytoplasmic localization of YAP in unstimulated ECs and, strikingly, blocked the nuclear import of YAP induced by Ab-induced HLA I activation in these cells and the increase in the expression of the YAP-regulated genes CTGF and CYR61 induced by HLA I stimulation. Our results identify the Src\/YAP axis as a key player in promoting the proliferation and migration of ECs that are critical in the pathogenesis of transplant vasculopathy.<\/jats:p>","DOI":"10.4049\/jimmunol.2000535","type":"journal-article","created":{"date-parts":[[2020,8,26]],"date-time":"2020-08-26T22:00:15Z","timestamp":1598479215000},"page":"1953-1961","source":"Crossref","is-referenced-by-count":8,"title":["Ligation of HLA Class I Molecules Induces YAP Activation through Src in Human Endothelial Cells"],"prefix":"10.1093","volume":"205","author":[{"given":"Tarique","family":"Anwar","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of California , Los Angeles, CA 90095"},{"name":"Department of Medicine, David Geffen School of Medicine, University of California , Los Angeles, CA 90095"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0074-7270","authenticated-orcid":false,"given":"James","family":"Sinnett-Smith","sequence":"additional","affiliation":[{"name":"Department of Medicine, David Geffen School of Medicine, University of California , Los Angeles, CA 90095"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6620-4274","authenticated-orcid":false,"given":"Yi-Ping","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of California , Los Angeles, CA 90095"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3524-545X","authenticated-orcid":false,"given":"Elaine F","family":"Reed","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of California , Los Angeles, CA 90095"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7838-9170","authenticated-orcid":false,"given":"Enrique","family":"Rozengurt","sequence":"additional","affiliation":[{"name":"Department of Medicine, David Geffen School of Medicine, University of California , Los Angeles, CA 90095"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,10,1]]},"reference":[{"key":"2025030417505238100_r1","doi-asserted-by":"crossref","first-page":"1748","DOI":"10.1111\/ajt.13242","article-title":"Blood vessels in allotransplantation","volume":"15","author":"Abrahimi","year":"2015","journal-title":"Am. 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