{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T14:14:11Z","timestamp":1781187251480,"version":"3.54.1"},"reference-count":50,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T00:00:00Z","timestamp":1588118400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health Research","award":["RP-PG-0310-1001 and 1003"],"award-info":[{"award-number":["RP-PG-0310-1001 and 1003"]}]},{"name":"The Natural Science Foundation of Guangdong Province","award":["2020A151501036"],"award-info":[{"award-number":["2020A151501036"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>P0-related protein (PZR), a Noonan and LEOPARD syndrome target, is a member of the transmembrane Immunoglobulin superfamily. Its cytoplasmic tail contains two immune-receptor tyrosine-based inhibitory motifs (ITIMs), implicated in adhesion-dependent signaling and regulating cell adhesion and motility. PZR promotes cell migration on the extracellular matrix (ECM) molecule, fibronectin, by interacting with SHP-2 (Src homology-2 domain-containing protein tyrosine phosphatase-2), a molecule essential for skeletal development and often mutated in Noonan and LEOPARD syndrome patients sharing overlapping musculoskeletal abnormalities and cardiac defects. To further explore the role of PZR, we assessed the expression of PZR and its ITIM-less isoform, PZRb, in human bone marrow mesenchymal stromal cells (hBM MSC), and its ability to facilitate adhesion to and spreading and migration on various ECM molecules. Furthermore, using siRNA knockdown, confocal microscopy, and immunoprecipitation assays, we assessed PZR and PZRb interactions with \u03b21 integrins. PZR was the predominant isoform in hBM MSC. Migrating hBM MSCs interacted most effectively with fibronectin and required the association of PZR, but not PZRb, with the integrin, VLA-5(\u03b15\u03b21), leading to modulation of focal adhesion kinase phosphorylation and vinculin levels. This raises the possibility that dysregulation of PZR function may modify hBM MSC migratory behavior, potentially contributing to skeletal abnormalities.<\/jats:p>","DOI":"10.3390\/cells9051100","type":"journal-article","created":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T13:23:45Z","timestamp":1588166625000},"page":"1100","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["P0-Related Protein Accelerates Human Mesenchymal Stromal Cell Migration by Modulating VLA-5 Interactions with Fibronectin"],"prefix":"10.3390","volume":"9","author":[{"given":"Maria G.","family":"Roubelakis","sequence":"first","affiliation":[{"name":"Laboratory of Biology, National and Kapodistrian University of Athens Medical School, 115 27 Athens, Greece"},{"name":"Stem Cell Research, Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9BQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grigorios","family":"Tsaknakis","sequence":"additional","affiliation":[{"name":"Stem Cell Research, Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9BQ, UK"},{"name":"Department of Hematology, School of Medicine, University of Crete, 70013 Heraklion, Crete, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng-Juan","family":"Lyu","sequence":"additional","affiliation":[{"name":"Stem Cell Research, Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9BQ, UK"},{"name":"South China University of Technology-the University of Western Australia Joint Centre for Regenerative Medicine Research, School of Medicine, South China University of Technology, Guangzhou 510006, China"},{"name":"Department of Orthopedics and Traumatology, Li Ka Shing Faculty of Medicine, University of Hong Kong, 102 Pok Fu Lam Road, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ourania","family":"Trohatou","sequence":"additional","affiliation":[{"name":"Laboratory of Biology, National and Kapodistrian University of Athens Medical School, 115 27 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew C. W.","family":"Zannettino","sequence":"additional","affiliation":[{"name":"Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide 5005, Australia"},{"name":"Cancer Program, Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide 5001, Australia"},{"name":"Central Adelaide Local Health Network, Adelaide 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne M.","family":"Watt","sequence":"additional","affiliation":[{"name":"Stem Cell Research, Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9BQ, UK"},{"name":"Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide 5005, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1210\/er.2017-00232","article-title":"The RASopathy family: Consequences of germline activation of the RAS\/MAPK pathway","volume":"39","author":"Tajan","year":"2018","journal-title":"Endocr. 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