{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T21:22:28Z","timestamp":1790112148683,"version":"4.0.1"},"reference-count":21,"publisher":"Portland Press Ltd.","issue":"1","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2008,4,1]]},"abstract":"<jats:p>We have recently shown that the C-type lectin-like receptor, CLEC-2, is expressed on platelets and that it mediates powerful platelet aggregation by the snake venom toxin rhodocytin. In addition, we have provided indirect evidence for an endogenous ligand for CLEC-2 in renal cells expressing HIV-1. This putative ligand facilitates transmission of HIV through its incorporation into the viral envelope and binding to CLEC-2 on platelets. The aim of the present study was to identify the ligand on these cells which binds to CLEC-2 on platelets. Recombinant CLEC-2 exhibits specific binding to HEK-293T (human embryonic kidney) cells in which the HIV can be grown. Furthermore, HEK-293T cells activate both platelets and CLEC-2-transfected DT-40 B-cells. The transmembrane protein podoplanin was identified on HEK-293T cells and was demonstrated to mediate both binding of HEK-293T cells to CLEC-2 and HEK-293T cell activation of CLEC-2-transfected DT-40 B-cells. Podoplanin is expressed on renal cells (podocytes). Furthermore, a direct interaction between CLEC-2 and podoplanin was confirmed using surface plasmon resonance and was shown to be independent of glycosylation of CLEC-2. The interaction has an affinity of 24.5\u00b13.7\u00a0\u03bcM. The present study identifies podoplanin as a ligand for CLEC-2 on renal cells.<\/jats:p>","DOI":"10.1042\/bj20071216","type":"journal-article","created":{"date-parts":[[2008,3,14]],"date-time":"2008-03-14T17:04:46Z","timestamp":1205514286000},"page":"133-140","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":102,"title":["Renal cells activate the platelet receptor CLEC-2 through podoplanin"],"prefix":"10.1042","volume":"411","author":[{"given":"Charita\u00a0M.","family":"Christou","sequence":"first","affiliation":[{"name":"Henry Wellcome Building for Molecular Physiology, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew\u00a0C.","family":"Pearce","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Sciences, Institute of Biomedical Research, The Medical School, University of Birmingham, Birmingham B15 2TT, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra\u00a0A.","family":"Watson","sequence":"additional","affiliation":[{"name":"Henry Wellcome Building for Molecular Physiology, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita\u00a0R.","family":"Mistry","sequence":"additional","affiliation":[{"name":"Henry Wellcome Building for Molecular Physiology, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice\u00a0Y.","family":"Pollitt","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Sciences, Institute of Biomedical Research, The Medical School, University of Birmingham, Birmingham B15 2TT, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angharad\u00a0E.","family":"Fenton-May","sequence":"additional","affiliation":[{"name":"Henry Wellcome Building for Molecular Physiology, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise\u00a0A.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David\u00a0G.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve\u00a0P.","family":"Watson","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Sciences, Institute of Biomedical Research, The Medical School, University of Birmingham, Birmingham B15 2TT, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris\u00a0A.","family":"O'callaghan","sequence":"additional","affiliation":[{"name":"Henry Wellcome Building for Molecular Physiology, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2008,3,13]]},"reference":[{"key":"2021112215105089800_B1","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1182\/blood-2005-05-1994","article-title":"A novel Syk-dependent mechanism of platelet activation by the C-type lectin receptor CLEC-2","volume":"107","author":"Suzuki-Inoue","year":"2006","journal-title":"Blood"},{"key":"2021112215105089800_B2","doi-asserted-by":"crossref","first-page":"12397","DOI":"10.1074\/jbc.M609558200","article-title":"The C-type lectin receptors CLEC-2 and Dectin-1, but not DC-SIGN, signal via a novel YXXL-dependent signaling cascade","volume":"282","author":"Fuller","year":"2007","journal-title":"J. Biol. Chem."},{"key":"2021112215105089800_B3","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1111\/j.1538-7836.2005.01429.x","article-title":"GPVI and integrin \u03b1IIb\u03b23 signaling in platelets","volume":"3","author":"Watson","year":"2005","journal-title":"J. Thromb. Haemostasis"},{"key":"2021112215105089800_B4","doi-asserted-by":"crossref","first-page":"3165","DOI":"10.1074\/jbc.M610383200","article-title":"The crystal structure and mutational binding analysis of the extracellular domain of the platelet-activating receptor CLEC-2","volume":"282","author":"Watson","year":"2007","journal-title":"J. Biol. Chem."},{"key":"2021112215105089800_B5","doi-asserted-by":"crossref","first-page":"8951","DOI":"10.1128\/JVI.00136-06","article-title":"DC-SIGN and CLEC-2 mediate human immunodeficiency virus type\u00a01 capture by platelets","volume":"80","author":"Chaipan","year":"2006","journal-title":"J. Virol."},{"key":"2021112215105089800_B6","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1038\/nm0502-522","article-title":"Replication and compartmentalization of HIV-1 in kidney epithelium of patients with HIV-associated nephropathy","volume":"8","author":"Marras","year":"2002","journal-title":"Nat. Med."},{"key":"2021112215105089800_B7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5414\/CNP61001","article-title":"Prevalence of proteinuria and the development of chronic kidney disease in HIV-infected patients","volume":"61","author":"Gupta","year":"2004","journal-title":"Clin. Nephrol."},{"key":"2021112215105089800_B8","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1107\/S1744309105037991","article-title":"Crystallization and X-ray diffraction analysis of human CLEC-2. Acta Crystallograph","volume":"61","author":"Watson","year":"2005","journal-title":"Sect. F Struct. Biol. Cryst. Commun."},{"key":"2021112215105089800_B9","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1016\/S0002-9440(10)62311-5","article-title":"Up-regulation of the lymphatic marker podoplanin, a mucin-type transmembrane glycoprotein, in human squamous cell carcinomas and germ cell tumors","volume":"166","author":"Schacht","year":"2005","journal-title":"Am. J. Pathol."},{"key":"2021112215105089800_B10","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1006\/abio.1998.2930","article-title":"BirA enzyme: production and application in the study of membrane receptor-ligand interactions by site-specific biotinylation","volume":"266","author":"O'Callaghan","year":"1999","journal-title":"Anal. Biochem."},{"key":"2021112215105089800_B11","doi-asserted-by":"crossref","first-page":"2601","DOI":"10.1182\/blood-2003-09-3319","article-title":"GPIb-dependent platelet activation is dependent on Src kinases but not MAP kinase or cGMP-dependent kinase","volume":"103","author":"Marshall","year":"2004","journal-title":"Blood"},{"key":"2021112215105089800_B12","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/S1074-7613(01)00187-X","article-title":"Molecular competition for NKG2D: H60 and RAE1 compete unequally for NKG2D with dominance of H60","volume":"15","author":"O'Callaghan","year":"2001","journal-title":"Immunity"},{"key":"2021112215105089800_B13","doi-asserted-by":"crossref","first-page":"25993","DOI":"10.1074\/jbc.M702327200","article-title":"Involvement of the snake toxin receptor CLEC-2 in podoplaninmediated platelet activation by cancer cells","volume":"282","author":"Suzuki-Inoue","year":"2007","journal-title":"J. Biol. Chem."},{"key":"2021112215105089800_B14","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1097\/01.ASN.0000078803.53165.C9","article-title":"Expression of podocyte-associated molecules in acquired human kidney diseases","volume":"14","author":"Koop","year":"2003","journal-title":"J. Am. Soc. Nephrol."},{"key":"2021112215105089800_B15","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1093\/ndt\/14.suppl_1.9","article-title":"Podoplanin, a novel 43-kDa membrane protein, controls the shape of podocytes","volume":"14","author":"Matsui","year":"1999","journal-title":"Nephrol. Dial. Transplant."},{"key":"2021112215105089800_B16","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1016\/j.bbrc.2006.08.171","article-title":"Inhibition of tumor cell-induced platelet aggregation using a novel anti-podoplanin antibody reacting with its platelet-aggregation-stimulating domain","volume":"349","author":"Kato","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2021112215105089800_B17","first-page":"1141","article-title":"Podoplanin, novel 43-kd membrane protein of glomerular epithelial cells, is down-regulated in puromycin nephrosis","volume":"151","author":"Breiteneder-Geleff","year":"1997","journal-title":"Am. J. Pathol."},{"key":"2021112215105089800_B18","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/0167-4889(88)90173-5","article-title":"Monoclonal antibodies specific to apical surfaces of rat alveolar type\u00a0I cells bind to surfaces of cultured, but not freshly isolated, type\u00a0II cells","volume":"970","author":"Dobbs","year":"1988","journal-title":"Biochim. Biophys. Acta"},{"key":"2021112215105089800_B19","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1002\/(SICI)1098-2744(199709)20:1<10::AID-MC3>3.0.CO;2-M","article-title":"Induction of PA2.26, a cell-surface antigen expressed by active fibroblasts, in mouse epidermal keratinocytes during carcinogenesis","volume":"20","author":"Gandarillas","year":"1997","journal-title":"Mol. Carcinog."},{"key":"2021112215105089800_B20","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/8756-3282(95)00457-2","article-title":"Characterization and cloning of the E11 antigen, a marker expressed by rat osteoblasts and osteocytes","volume":"18","author":"Wetterwald","year":"1996","journal-title":"Bone"},{"key":"2021112215105089800_B21","first-page":"270","article-title":"Podoplanin: a specific marker for lymphatic endothelium expressed in angiosarcoma","volume":"83","author":"Breiteneder-Geleff","year":"1999","journal-title":"Verh. Dtsch. Ges. Pathol."}],"container-title":["Biochemical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/411\/1\/133\/651479\/bj4110133.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/411\/1\/133\/651479\/bj4110133.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T20:10:56Z","timestamp":1637611856000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemj\/article\/411\/1\/133\/44578\/Renal-cells-activate-the-platelet-receptor-CLEC-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,3,13]]},"references-count":21,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2008,4,1]]}},"URL":"https:\/\/doi.org\/10.1042\/bj20071216","relation":{},"ISSN":["0264-6021","1470-8728"],"issn-type":[{"value":"0264-6021","type":"print"},{"value":"1470-8728","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,3,13]]}}}