{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T02:11:40Z","timestamp":1779243100290,"version":"3.51.4"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2000,9,1]],"date-time":"2000-09-01T00:00:00Z","timestamp":967766400000},"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":[[2000,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The TCR is a constitutively recycling receptor meaning that a constant fraction of TCR from the plasma membrane is transported inside the cell at the same time as a constant fraction of TCR from the intracellular pool is transported to the plasma membrane. TCR recycling is affected by protein kinase C activity. Thus, an increase in protein kinase C activity affects TCR recycling kinetics leading to a new TCR equilibrium with a reduced level of TCR expressed at the T cell surface. Down-regulation of TCR expression compromises T cell activation. Conversely, TCR up-regulation is expected to increase T cell responsiveness. The purpose of this study was to identify and characterize potential pathways for TCR up-regulation. We found that ceramide affected TCR recycling dynamics and induced TCR up-regulation in a concentration- and time-dependent manner. Experiments applying phosphatase inhibitors indicated that ceramide-induced TCR up-regulation was most probably mediated by serine\/threonine protein phosphatase 2A. Analyses of T cell variants demonstrated that TCR up-regulation was dependent on the presence of an intact CD3\u03b3 L-based motif and thus acted on TCR engaged in the recycling pathway. Finally, we showed that TCR up-regulation probably plays a physiological role by increasing T cell responsiveness. Thus, by affecting the TCR recycling kinetics, T cells have the potential both to up- and down-regulate TCR expression and thereby adjust T cell responsiveness.<\/jats:p>","DOI":"10.4049\/jimmunol.165.6.3065","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T21:30:49Z","timestamp":1398029449000},"page":"3065-3072","source":"Crossref","is-referenced-by-count":15,"title":["Ceramide-Induced TCR Up-Regulation"],"prefix":"10.1093","volume":"165","author":[{"given":"Charlotte","family":"Menne\u0301","sequence":"first","affiliation":[{"name":"Institute of Medical Microbiology and Immunology, University of Copenhagen , Copenhagen ,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens Peter H","family":"Lauritsen","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology and Immunology, University of Copenhagen , Copenhagen ,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jes","family":"Dietrich","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology and Immunology, University of Copenhagen , Copenhagen ,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jesper","family":"Kastrup","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology and Immunology, University of Copenhagen , Copenhagen ,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne-Marie K","family":"Wegener","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology and Immunology, University of Copenhagen , Copenhagen ,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niels","family":"\u00d8dum","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology and Immunology, University of Copenhagen , Copenhagen ,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carsten","family":"Geisler","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology and Immunology, University of Copenhagen , Copenhagen ,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2000,9,15]]},"reference":[{"key":"2026020213090581900_R1","first-page":"104","volume-title":"Science","year":"1996"},{"key":"2026020213090581900_R2","first-page":"271","volume-title":"J. Cell Biol.","year":"1997"},{"key":"2026020213090581900_R3","first-page":"24232","volume-title":"J. Biol. Chem.","year":"1998"},{"key":"2026020213090581900_R4","first-page":"5764","volume-title":"J. Immunol.","year":"1999"},{"key":"2026020213090581900_R5","first-page":"13342","volume-title":"J. Biol. Chem.","year":"1987"},{"key":"2026020213090581900_R6","first-page":"1141","volume-title":"J. Exp. Med.","year":"1987"},{"key":"2026020213090581900_R7","first-page":"1623","volume-title":"Eur. J. Immunol.","year":"1991"},{"key":"2026020213090581900_R8","first-page":"2156","volume-title":"EMBO J.","year":"1994"},{"key":"2026020213090581900_R9","first-page":"260","volume-title":"J. Immunol.","year":"1998"},{"key":"2026020213090581900_R10","first-page":"1581","volume-title":"J. Exp. Med.","year":"1999"},{"key":"2026020213090581900_R11","first-page":"5149","volume-title":"J. Immunol.","year":"1999"},{"key":"2026020213090581900_R12","first-page":"2059","volume-title":"J. Exp. Med.","year":"1995"},{"key":"2026020213090581900_R13","first-page":"519","volume-title":"Science","year":"1993"},{"key":"2026020213090581900_R14","first-page":"17762","volume-title":"J. Biol. Chem.","year":"1993"},{"key":"2026020213090581900_R15","first-page":"765","volume-title":"Cell","year":"1992"},{"key":"2026020213090581900_R16","first-page":"3125","volume-title":"J. Biol. Chem.","year":"1994"},{"key":"2026020213090581900_R17","first-page":"15523","volume-title":"J. Biol. Chem.","year":"1993"},{"key":"2026020213090581900_R18","first-page":"11232","volume-title":"Biochemistry","year":"1998"},{"key":"2026020213090581900_R19","first-page":"18431","volume-title":"J. Biol. Chem.","year":"1996"},{"key":"2026020213090581900_R20","first-page":"273","volume-title":"Biochim. Biophys. Acta","year":"1996"},{"key":"2026020213090581900_R21","first-page":"233","volume-title":"Biochim. Biophys. Acta","year":"1998"},{"key":"2026020213090581900_R22","first-page":"2037","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1991"},{"key":"2026020213090581900_R23","first-page":"2437","volume-title":"J. Immunol.","year":"1992"},{"key":"2026020213090581900_R24","first-page":"26281","volume-title":"J. Biol. Chem.","year":"1998"},{"key":"2026020213090581900_R25","first-page":"685","volume-title":"Scand. J. Immunol.","year":"1988"},{"key":"2026020213090581900_R26","first-page":"125","volume-title":"Biochem. J.","year":"1997"},{"key":"2026020213090581900_R27","first-page":"4915","volume-title":"EMBO J.","year":"1999"},{"key":"2026020213090581900_R28","first-page":"11441","volume-title":"J. Biol. Chem.","year":"1996"},{"key":"2026020213090581900_R29","first-page":"19605","volume-title":"J. Biol. Chem.","year":"1994"},{"key":"2026020213090581900_R30","first-page":"21375","volume-title":"J. Biol. Chem.","year":"1996"},{"key":"2026020213090581900_R31","first-page":"13169","volume-title":"J. Biol. Chem.","year":"1996"},{"key":"2026020213090581900_R32","first-page":"27730","volume-title":"J. Biol. Chem.","year":"1997"},{"key":"2026020213090581900_R33","first-page":"325","volume-title":"Cell","year":"1994"},{"key":"2026020213090581900_R34","first-page":"3125","volume-title":"J. Biol. Chem.","year":"1994"},{"key":"2026020213090581900_R35","first-page":"82","volume-title":"Nature","year":"1998"},{"key":"2026020213090581900_R36","first-page":"148","volume-title":"Nature","year":"1995"},{"key":"2026020213090581900_R37","first-page":"299","volume-title":"Immunol. Today","year":"1997"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/165\/6\/3065\/62131928\/3065.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/165\/6\/3065\/62131928\/3065.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T18:14:15Z","timestamp":1770056055000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/165\/6\/3065\/8038564"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,9]]},"references-count":37,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2000,9,15]]},"published-print":{"date-parts":[[2000,9,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.165.6.3065","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2000,9]]},"published":{"date-parts":[[2000,9]]}}}