{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T13:01:55Z","timestamp":1791810115792,"version":"4.3.4"},"reference-count":31,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,2,6]],"date-time":"2021-02-06T00:00:00Z","timestamp":1612569600000},"content-version":"vor","delay-in-days":36,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001802","name":"University of Canberra","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001802","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002387","name":"National Cancer Institute, Cairo University","doi-asserted-by":"publisher","award":["3R01"],"award-info":[{"award-number":["3R01"]}],"id":[{"id":"10.13039\/501100002387","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002387","name":"National Cancer Institute, Cairo University","doi-asserted-by":"publisher","award":["BF"],"award-info":[{"award-number":["BF"]}],"id":[{"id":"10.13039\/501100002387","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002387","name":"National Cancer Institute, Cairo University","doi-asserted-by":"publisher","award":["R01 CA208669-01A1"],"award-info":[{"award-number":["R01 CA208669-01A1"]}],"id":[{"id":"10.13039\/501100002387","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007707","name":"University of California, Davis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007707","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["jbc.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Biological Chemistry"],"published-print":{"date-parts":[[2021,1]]},"DOI":"10.1016\/j.jbc.2021.100399","type":"journal-article","created":{"date-parts":[[2021,2,17]],"date-time":"2021-02-17T23:15:11Z","timestamp":1613603711000},"page":"100399","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":30,"special_numbering":"C","title":["Soluble CD40L activates soluble and cell-surface integrin \u03b1v\u03b23, \u03b15\u03b21, and \u03b14\u03b21 by binding to the allosteric ligand-binding site (site 2)"],"prefix":"10.1016","volume":"296","author":[{"given":"Yoko K.","family":"Takada","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiko","family":"Shimoda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanual","family":"Maverakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7773-5254","authenticated-orcid":false,"given":"Brunie H.","family":"Felding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Holland","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshikazu","family":"Takada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jbc.2021.100399_bib1","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1038\/31002","article-title":"T-cell help for cytotoxic T lymphocytes is mediated by CD40-CD40L interactions","volume":"393","author":"Schoenberger","year":"1998","journal-title":"Nature"},{"key":"10.1016\/j.jbc.2021.100399_bib2","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/361539a0","article-title":"Defective expression of T-cell CD40 ligand causes X-linked immunodeficiency with hyper-IgM","volume":"361","author":"Korthauer","year":"1993","journal-title":"Nature"},{"key":"10.1016\/j.jbc.2021.100399_bib3","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1007\/PL00000776","article-title":"The CD40\/CD154 receptor\/ligand dyad","volume":"58","author":"Schonbeck","year":"2001","journal-title":"Cell Mol. Life Sci."},{"key":"10.1016\/j.jbc.2021.100399_bib4","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1002\/biof.62","article-title":"CD40\/CD40L signaling and its implication in health and disease","volume":"35","author":"Chatzigeorgiou","year":"2009","journal-title":"Biofactors"},{"key":"10.1016\/j.jbc.2021.100399_bib5","doi-asserted-by":"crossref","first-page":"273","DOI":"10.3346\/jkms.2000.15.3.273","article-title":"Activated platelets induce secretion of interleukin-1beta, monocyte chemotactic protein-1, and macrophage inflammatory protein-1alpha and surface expression of intercellular adhesion molecule-1 on cultured endothelial cells","volume":"15","author":"Cha","year":"2000","journal-title":"J.\u00a0Korean Med. Sci."},{"key":"10.1016\/j.jbc.2021.100399_bib6","doi-asserted-by":"crossref","first-page":"2559","DOI":"10.1096\/fj.06-6265fje","article-title":"Platelets induce differentiation of human CD34+ progenitor cells into foam cells and endothelial cells","volume":"20","author":"Daub","year":"2006","journal-title":"FASEB J."},{"key":"10.1016\/j.jbc.2021.100399_bib7","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1038\/35393","article-title":"CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells","volume":"391","author":"Henn","year":"1998","journal-title":"Nature"},{"key":"10.1016\/j.jbc.2021.100399_bib8","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1097\/00002281-200109000-00004","article-title":"Regulation of CD40 ligand expression in systemic lupus erythematosus","volume":"13","author":"Crow","year":"2001","journal-title":"Curr. Opin. Rheumatol."},{"key":"10.1016\/j.jbc.2021.100399_bib9","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1111\/j.1523-1755.2005.00663.x","article-title":"Activation of mesangial cells by platelets in systemic lupus erythematosus via a CD154-dependent induction of CD40","volume":"68","author":"Delmas","year":"2005","journal-title":"Kidney Int."},{"key":"10.1016\/j.jbc.2021.100399_bib10","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1146\/annurev.immunol.16.1.111","article-title":"CD40 and CD154 in cell-mediated immunity","volume":"16","author":"Grewal","year":"1998","journal-title":"Annu. Rev. Immunol."},{"key":"10.1016\/j.jbc.2021.100399_bib11","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1038\/nm0302-247","article-title":"CD40L stabilizes arterial thrombi by a beta3 integrin--dependent mechanism","volume":"8","author":"Andre","year":"2002","journal-title":"Nat. Med."},{"key":"10.1016\/j.jbc.2021.100399_bib12","doi-asserted-by":"crossref","first-page":"18055","DOI":"10.1074\/jbc.M111.333989","article-title":"Functional interaction of CD154 protein with alpha5beta1 integrin is totally independent from its binding to alphaIIbbeta3 integrin and CD40 molecules","volume":"287","author":"El Fakhry","year":"2012","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.jbc.2021.100399_bib13","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.4049\/jimmunol.1801630","article-title":"Integrin binding to the trimeric interface of CD40L plays a critical role in CD40\/CD40L signaling","volume":"203","author":"Takada","year":"2019","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.jbc.2021.100399_bib14","doi-asserted-by":"crossref","first-page":"e96372","DOI":"10.1371\/journal.pone.0096372","article-title":"The chemokine fractalkine can activate integrins without CX3CR1 through direct binding to a ligand-binding site distinct from the classical RGD-binding site","volume":"9","author":"Fujita","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.jbc.2021.100399_bib15","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1074\/jbc.M114.579946","article-title":"Proinflammatory secreted phospholipase A2 type IIA (sPLA-IIA) induces integrin activation through direct binding to a newly identified binding site (site 2) in integrins alphavbeta3, alpha4beta1, and alpha5beta1","volume":"290","author":"Fujita","year":"2015","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.jbc.2021.100399_bib16","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1042\/BCJ20170867","article-title":"Stromal cell-derived factor-1 (CXCL12) activates integrins by direct binding to an allosteric ligand-binding site (site 2) of integrins without CXCR4","volume":"475","author":"Fujita","year":"2018","journal-title":"Biochem. J."},{"key":"10.1016\/j.jbc.2021.100399_bib17","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1038\/s41467-019-09453-x","article-title":"Integrin activation by the lipid molecule 25-hydroxycholesterol induces a proinflammatory response","volume":"10","author":"Pokharel","year":"2019","journal-title":"Nat. Commun."},{"key":"10.1016\/j.jbc.2021.100399_bib18","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1186\/1471-2105-14-346","article-title":"Disulfide by Design 2.0: A web-based tool for disulfide engineering in proteins","volume":"14","author":"Craig","year":"2013","journal-title":"BMC Bioinformatics"},{"key":"10.1016\/j.jbc.2021.100399_bib19","doi-asserted-by":"crossref","first-page":"18066","DOI":"10.1074\/jbc.M801213200","article-title":"Direct binding of integrin alphavbeta3 to FGF1 plays a role in FGF1 signaling","volume":"283","author":"Mori","year":"2008","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.jbc.2021.100399_bib20","doi-asserted-by":"crossref","first-page":"24106","DOI":"10.1074\/jbc.M109.013201","article-title":"The direct binding of insulin-like growth factor-1 (IGF-1) to integrin alphavbeta3 is involved in IGF-1 signaling","volume":"284","author":"Saegusa","year":"2009","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.jbc.2021.100399_bib21","doi-asserted-by":"crossref","first-page":"31388","DOI":"10.1074\/jbc.M110.113878","article-title":"Direct binding of the EGF-like domain of neuregulin-1 to integrins ({alpha}v{beta}3 and {alpha}6{beta}4) is involved in neuregulin-1\/ErbB signaling","volume":"285","author":"Ieguchi","year":"2010","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.jbc.2021.100399_bib22","doi-asserted-by":"crossref","first-page":"5809","DOI":"10.4049\/jimmunol.1200889","article-title":"Integrins alphavbeta3 and alpha4beta1 act as coreceptors for fractalkine, and the integrin-binding defective mutant of fractalkine is an antagonist of CX3CR1","volume":"189","author":"Fujita","year":"2012","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.jbc.2021.100399_bib23","doi-asserted-by":"crossref","first-page":"20067","DOI":"10.1074\/jbc.M117.818302","article-title":"Direct binding to integrins and loss of disulfide linkage in interleukin-1beta (IL-1beta) are involved in the agonistic action of IL-1beta","volume":"292","author":"Takada","year":"2017","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.jbc.2021.100399_bib24","doi-asserted-by":"crossref","first-page":"26107","DOI":"10.1074\/jbc.M804835200","article-title":"Pro-inflammatory secretory phospholipase A2 type IIA binds to integrins alphavbeta3 and alpha4beta1 and induces proliferation of monocytic cells in an integrin-dependent manner","volume":"283","author":"Saegusa","year":"2008","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.jbc.2021.100399_bib25","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1038\/nrm2871","article-title":"The final steps of\u00a0integrin activation: The end game","volume":"11","author":"Shattil","year":"2010","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.jbc.2021.100399_bib26","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/nrm3624","article-title":"Talins and kindlins: Partners in integrin-mediated adhesion","volume":"14","author":"Calderwood","year":"2013","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.jbc.2021.100399_bib27","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.1074\/jbc.M109.057349","article-title":"Integrin alphaIIbbeta3 activation in Chinese hamster ovary cells and platelets increases clustering rather than affinity","volume":"285","author":"Bunch","year":"2010","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.jbc.2021.100399_bib28","doi-asserted-by":"crossref","first-page":"4712","DOI":"10.1038\/emboj.2011.333","article-title":"Regulation of integrin affinity on cell surfaces","volume":"30","author":"Schurpf","year":"2011","journal-title":"EMBO J."},{"key":"10.1016\/j.jbc.2021.100399_bib29","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/87569","article-title":"C-terminal opening mimics 'inside-out' activation of integrin alpha5beta1","volume":"8","author":"Takagi","year":"2001","journal-title":"Nat. Struct. Biol."},{"key":"10.1016\/j.jbc.2021.100399_bib30","doi-asserted-by":"crossref","first-page":"5872","DOI":"10.1021\/bi9827619","article-title":"Specific binding of integrin alpha v beta 3 to the fibrinogen gamma and alpha E chain C-terminal domains","volume":"38","author":"Yokoyama","year":"1999","journal-title":"Biochemistry"},{"key":"10.1016\/j.jbc.2021.100399_bib31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0378-1119(88)90219-3","article-title":"Secreted placental alkaline phosphatase: A powerful new quantitative indicator of gene expression in eukaryotic cells","volume":"66","author":"Berger","year":"1988","journal-title":"Gene"}],"container-title":["Journal of Biological Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S002192582100171X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S002192582100171X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2021,10,17]],"date-time":"2021-10-17T04:01:47Z","timestamp":1634443307000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S002192582100171X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":31,"alternative-id":["S002192582100171X"],"URL":"https:\/\/doi.org\/10.1016\/j.jbc.2021.100399","relation":{},"ISSN":["0021-9258"],"issn-type":[{"value":"0021-9258","type":"print"}],"subject":[],"published":{"date-parts":[[2021,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Soluble CD40L activates soluble and cell-surface integrin \u03b1v\u03b23, \u03b15\u03b21, and \u03b14\u03b21 by binding to the allosteric ligand-binding site (site 2)","name":"articletitle","label":"Article Title"},{"value":"Journal of Biological Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jbc.2021.100399","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 The Authors. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology.","name":"copyright","label":"Copyright"}],"article-number":"100399"}}