{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T18:00:08Z","timestamp":1770746408629,"version":"3.49.0"},"reference-count":26,"publisher":"Rockefeller University Press","issue":"7","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1998,10,5]]},"abstract":"<jats:p>L-selectin binding activity for its ligand expressed by vascular endothelium is rapidly and transiently increased after leukocyte activation. To identify mechanisms for upregulation and assess how this influences leukocyte\/endothelial cell interactions, cell-surface dimers of L-selectin were induced using the coumermycin\u2013GyrB dimerization strategy for cross-linking L-selectin cytoplasmic domains in L-selectin cDNA-transfected lymphoblastoid cells. Coumermycin- induced L-selectin dimerization resulted in an approximately fourfold increase in binding of phosphomanan monoester core complex (PPME), a natural mimic of an L-selectin ligand, comparable to that observed after leukocyte activation. Moreover, L-selectin dimerization significantly increased (by \u223c700%) the number of lymphocytes rolling on vascular endothelium under a broad range of physiological shear stresses, and significantly slowed their rolling velocities. Therefore, L-selectin dimerization may explain the rapid increase in ligand binding activity that occurs after leukocyte activation and may directly influence leukocyte migration to peripheral lymphoid tissues or to sites of inflammation. Inducible oligomerization may also be a common mechanism for rapidly upregulating the adhesive or ligand-binding function of other cell-surface receptors.<\/jats:p>","DOI":"10.1084\/jem.188.7.1385","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:49:30Z","timestamp":1027702170000},"page":"1385-1390","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":51,"title":["Regulation of L-Selectin\u2013mediated Rolling through Receptor Dimerization"],"prefix":"10.1084","volume":"188","author":[{"given":"Xuan","family":"Li","sequence":"first","affiliation":[{"name":"From the *Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710; and \u2021Merck Co., Inc., Rahway, New Jersey 07065"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas A.","family":"Steeber","sequence":"additional","affiliation":[{"name":"From the *Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710; and \u2021Merck Co., Inc., Rahway, New Jersey 07065"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mimi L.K.","family":"Tang","sequence":"additional","affiliation":[{"name":"From the *Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710; and \u2021Merck Co., Inc., Rahway, New Jersey 07065"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael A.","family":"Farrar","sequence":"additional","affiliation":[{"name":"From the *Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710; and \u2021Merck Co., Inc., Rahway, New Jersey 07065"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roger M.","family":"Perlmutter","sequence":"additional","affiliation":[{"name":"From the *Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710; and \u2021Merck Co., Inc., Rahway, New Jersey 07065"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas F.","family":"Tedder","sequence":"additional","affiliation":[{"name":"From the *Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710; and \u2021Merck Co., Inc., Rahway, New Jersey 07065"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[1998,10,5]]},"reference":[{"key":"2023072508225267500_B1","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/0955-0674(94)90092-2","article-title":"The selectins and their ligands","volume":"6","author":"Rosen","year":"1994","journal-title":"Curr Opin Cell Biol"},{"key":"2023072508225267500_B2","first-page":"866","article-title":"The selectins: vascular adhesion molecules","volume":"9","author":"Tedder","year":"1995","journal-title":"FASEB (Fed Am Soc Exp Biol) J"},{"key":"2023072508225267500_B3","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1038\/349691a0","article-title":"Regulation of leukocyte migration by activation of the leukocyte adhesion molecule-1 (LAM-1) selectin","volume":"349","author":"Spertini","year":"1991","journal-title":"Nature"},{"key":"2023072508225267500_B4","doi-asserted-by":"crossref","first-page":"13961","DOI":"10.1074\/jbc.272.21.13961","article-title":"Chemoattractant receptor-induced phosphorylation of L-selectin","volume":"272","author":"Haribabu","year":"1997","journal-title":"J Biol Chem"},{"key":"2023072508225267500_B5","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1016\/0092-8674(91)90438-5","article-title":"The neutrophil selectin LECAM-1 presents carbohydrate ligands to the vascular selectins ELAM-1 and GMP-140","volume":"66","author":"Picker","year":"1991","journal-title":"Cell"},{"key":"2023072508225267500_B6","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1177\/41.3.7679125","article-title":"Detection and spatial distribution of the beta 2 integrin (Mac-1) and L-selectin (LECAM-1) adherence receptors on human neutrophils by high-resolution field emission SEM","volume":"41","author":"Erlandsen","year":"1993","journal-title":"J Histochem Cytochem"},{"key":"2023072508225267500_B7","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/0092-8674(95)90278-3","article-title":"A central role for microvillus receptor presentation in leukocyte adhesion under flow","volume":"82","author":"von Andrian","year":"1995","journal-title":"Cell"},{"key":"2023072508225267500_B8","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1084\/jem.177.3.833","article-title":"Regulation of leukocyte rolling and adhesion to HEV through the cytoplasm domain of L-selectin","volume":"177","author":"Kansas","year":"1993","journal-title":"J Exp Med"},{"key":"2023072508225267500_B9","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1083\/jcb.129.4.1155","article-title":"The cytoplasmic domain of L-selectin interacts with cytoskeletal proteins via alpha- actinin: receptor positioning in microvilli does not require interaction with alpha-actinin","volume":"129","author":"Pavalko","year":"1995","journal-title":"J Cell Biol"},{"key":"2023072508225267500_B10","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1038\/383178a0","article-title":"Activation of the Raf-1 kinase cascade by coumermycin- induced dimerization","volume":"383","author":"Farrar","year":"1996","journal-title":"Nature"},{"key":"2023072508225267500_B11","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1084\/jem.170.1.123","article-title":"Isolation and chromosomal localization of cDNAs encoding a novel human lymphocyte cell-surface molecule, LAM1: homology with the mouse lymphocyte homing receptor and other human adhesion proteins","volume":"170","author":"Tedder","year":"1989","journal-title":"J Exp Med"},{"key":"2023072508225267500_B12","doi-asserted-by":"crossref","first-page":"532","DOI":"10.4049\/jimmunol.144.2.532","article-title":"Expression of the human leukocyte adhesion molecule, LAM1. Identity with the TQ1 and Leu-8 differentiation antigens","volume":"144","author":"Tedder","year":"1990","journal-title":"J Immunol"},{"key":"2023072508225267500_B13","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1083\/jcb.125.6.1417","article-title":"Monocyte rolling, arrest, and spreading on IL-4\u2013activated vascular endothelium under flow is mediated via sequential action of L-selectin, \u03b21-integrins, and \u03b22-integrins","volume":"125","author":"Luscinskas","year":"1994","journal-title":"J Cell Biol"},{"key":"2023072508225267500_B14","doi-asserted-by":"crossref","first-page":"3734","DOI":"10.1073\/pnas.80.12.3734","article-title":"Permanent cell line expressing factor VIII\u2013related antigen established by hybridization","volume":"80","author":"Edgell","year":"1983","journal-title":"Proc Natl Acad Sci USA"},{"key":"2023072508225267500_B15","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/0003-2697(83)90590-0","article-title":"Preparation and properties of fluorescent polysaccharides","volume":"130","author":"Glabe","year":"1983","journal-title":"Anal Biochem"},{"key":"2023072508225267500_B16","doi-asserted-by":"crossref","first-page":"952","DOI":"10.4049\/jimmunol.159.2.952","article-title":"Ligation of L-selectin through conserved regions within the lectin domain activates signal transduction pathways and integrin function in human, mouse and rat leukocytes","volume":"159","author":"Steeber","year":"1997","journal-title":"J Immunol"},{"key":"2023072508225267500_B17","doi-asserted-by":"crossref","first-page":"2565","DOI":"10.4049\/jimmunol.147.8.2565","article-title":"Leukocyte adhesion molecule-1 (LAM-1, L-selectin) interacts with an inducible endothelial cell ligand to support leukocyte adhesion","volume":"147","author":"Spertini","year":"1991","journal-title":"J Immunol"},{"key":"2023072508225267500_B18","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/379266a0","article-title":"Adhesion through L-selectin requires a threshold hydrodynamic shear","volume":"379","author":"Finger","year":"1996","journal-title":"Nature"},{"key":"2023072508225267500_B19","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1083\/jcb.136.3.717","article-title":"Threshold levels of fluid shear promote leukocyte adhesion through selectins (CD62L, P, E)","volume":"136","author":"Lawrence","year":"1997","journal-title":"J Cell Biol"},{"key":"2023072508225267500_B20","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1016\/S0006-3495(92)81660-0","article-title":"How do selectins mediate leukocyte rolling in venules?","volume":"63","author":"T\u00f6zeren","year":"1992","journal-title":"Biophys J"},{"key":"2023072508225267500_B21","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/374539a0","article-title":"Lifetime of the P-selectin\u2013carbohydrate bond and its response to tensile force in hydrodynamic flow","volume":"374","author":"Alon","year":"1995","journal-title":"Nature"},{"key":"2023072508225267500_B22","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1083\/jcb.138.5.1169","article-title":"The kinetics of L-selectin tethers and the mechanics of selectin-mediated rolling","volume":"138","author":"Alon","year":"1997","journal-title":"J Cell Biol"},{"key":"2023072508225267500_B23","doi-asserted-by":"crossref","first-page":"15229","DOI":"10.1016\/S0021-9258(18)82460-7","article-title":"Structural and functional characterization of monomeric soluble P-selectin and comparison with membrane P-selectin","volume":"268","author":"Ushiyama","year":"1993","journal-title":"J Biol Chem"},{"key":"2023072508225267500_B24","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1074\/jbc.273.2.763","article-title":"Affinity and kinetic analysis of L-selectin (CD62L) binding to glycosylation-dependent cell-adhesion molecule-1","volume":"273","author":"Nicholson","year":"1998","journal-title":"J Biol Chem"},{"key":"2023072508225267500_B25","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1146\/annurev.bi.65.070196.002301","article-title":"Structural basis of lectin-carbohydrate recognition","volume":"65","author":"Weis","year":"1996","journal-title":"Annu Rev Biochem"},{"key":"2023072508225267500_B26","doi-asserted-by":"crossref","first-page":"5113","DOI":"10.4049\/jimmunol.160.10.5113","article-title":"Intrinsic differences in L-selectin expression levels affect T and B lymphocyte subset-specific recirculation pathways","volume":"160","author":"Tang","year":"1998","journal-title":"J Immunol"}],"container-title":["The Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/188\/7\/1385\/1691339\/98-1024.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/188\/7\/1385\/1691339\/98-1024.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T09:32:48Z","timestamp":1690277568000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/188\/7\/1385\/7749\/Regulation-of-L-Selectin-mediated-Rolling-through"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,10,5]]},"references-count":26,"journal-issue":{"issue":"7","published-print":{"date-parts":[[1998,10,5]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.188.7.1385","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,10,5]]}}}