title: A cell death pathway induced by antibody-mediated cross-linking of CD45 on lymphocytes.
abstract: The protein tyrosine phosphatase CD45 is a highly expressed glycoprotein present on all nucleated cells of hematopoietic origin. To date, all the functions attributed to CD45 are inherently coupled to its phosphatase activity. For instance, the regulation of lymphocyte antigen receptor signaling is mediated through the dephosphorylation, and hence activation, of Src-family kinases by CD45. Moreover, signaling via cytokine receptors is negatively modulated by CD45 by dephosphorylation of Janus kinase family members. Recently, another function for CD45, unrelated to regulation of surface receptor signaling, has been unraveled. Specific engagement of CD45 by monoclonal antibodies at the surface of lymphocytes induced their death, through an alternative caspase-independent pathway. In striking contrast to all other previously reported functions for CD45, its phosphatase activity is completely dispensable for the induction of cell death. This article reviews the current knowledge on the death pathway triggered by CD45 ligation on lymphocytes. In an attempt to better elucidate the mechanism of cell death induction through CD45, we also provide original data regarding the susceptibility of various subsets of immature and mature T and B cells to death induced by CD45 engagement. The physiological significance and therapeutic potential of CD45-induced death are also discussed.
authors.affiliation: MetrioGene Biosciences Inc., 6100 Royalmount Av., Montreal, QC, Canada, H4P 2R2. asteff@metrriogene.com
authors.forename: Ann-Muriel
authors.initials: AM
authors.lastname: Steff
authors.forename: Marylène
authors.initials: M
authors.lastname: Fortin
authors.forename: Fabianne
authors.initials: F
authors.lastname: Philippoussis
authors.forename: Sylvie
authors.initials: S
authors.lastname: Lesage
authors.forename: Chantal
authors.initials: C
authors.lastname: Arguin
authors.forename: Pauline
authors.initials: P
authors.lastname: Johnson
authors.forename: Patrice
authors.initials: P
authors.lastname: Hugo
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D017209:Apoptosis / Q000276:immunology*; D003432:Cross-Linking Reagents; D037483:Galectin 1 / Q000378:metabolism; D006801:Humans; D017493:Leukocyte Common Antigens / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D008024:Ligands; D008214:Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D015398:Signal Transduction
chemical_list: D000911:Antibodies, Monoclonal; D003432:Cross-Linking Reagents; D037483:Galectin 1; D008024:Ligands; D017493:Leukocyte Common Antigens