{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T02:27:30Z","timestamp":1770085650419,"version":"3.49.0"},"reference-count":73,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2001,10,1]],"date-time":"2001-10-01T00:00:00Z","timestamp":1001894400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2001,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>L-selectin (CD62L), a lectin-like adhesion molecule, mediates lymphocyte homing and leukocyte accumulation at sites of inflammation. Its transmembrane (TM) and intracellular (IC) domains confer clustering of L-selectin on microvilli of resting leukocytes, which is important for L-selectin function. Following activation of protein kinase C (PKC) or calmodulin inhibition, the wild-type (WT) protein is rapidly cleaved in its membrane-proximal ectodomain. To examine whether L-selectin topography or TM\/IC domains are involved in this shedding process, we used stable transfectants expressing WT L-selectin (on microvilli) or chimeric molecules consisting of the L-selectin ectodomain linked to the TM\/IC domains of CD44 (excluded from microvilli) or CD31 (randomly distributed). PKC activation by PMA altered the cells\u2019 surface morphology, but did not induce a redistribution of L-selectin ectodomains. All cell lines shed ectodomains upon PMA activation in a dose-dependent fashion and with similar kinetics. Calmodulin inhibition by trifluoperazine induced shedding in both WT and chimera transfectants. At high trifluoperazine concentrations, shedding of WT L-selectin was significantly more pronounced than that of chimeric molecules. Regardless of the activating stimulus, shedding was blocked by a hydroxamate-based metalloprotease inhibitor, suggesting that ectodomain down-regulation occurred through proteolytic cleavage by identical protease(s). These results show that the recognition site(s) for PKC-induced L-selectin shedding is exclusively contained within the ectodomain; the nature of subsurface structures and surface topography are irrelevant. Shedding induced by calmodulin inhibition has two components: one requires the L-selectin TM\/IC domain, and the other is independent of it.<\/jats:p>","DOI":"10.4049\/jimmunol.167.7.3642","type":"journal-article","created":{"date-parts":[[2014,4,21]],"date-time":"2014-04-21T23:21:00Z","timestamp":1398122460000},"page":"3642-3651","source":"Crossref","is-referenced-by-count":18,"title":["L-Selectin Shedding Is Independent of Its Subsurface Structures and Topographic Distribution"],"prefix":"10.1093","volume":"167","author":[{"given":"Brian P","family":"Fors","sequence":"first","affiliation":[{"name":"Center for Blood Research and Department of Pathology, Harvard Medical School , Boston, MA 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katayoon","family":"Goodarzi","sequence":"additional","affiliation":[{"name":"Center for Blood Research and Department of Pathology, Harvard Medical School , Boston, MA 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrich H","family":"von Andrian","sequence":"additional","affiliation":[{"name":"Center for Blood Research and Department of Pathology, Harvard Medical School , Boston, MA 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2001,10,1]]},"reference":[{"key":"2026020208115680100_R1","first-page":"1033","volume-title":"Cell","year":"1991"},{"key":"2026020208115680100_R2","first-page":"301","volume-title":"Cell","year":"1994"},{"key":"2026020208115680100_R3","first-page":"1020","volume-title":"N. 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