Apoptosis mediated through CD45 is independent of its phosphatase activity and association with leukocyte phosphatase-associated phosphoprotein.
Besides the well-recognized role of CD45 as a major player in TCR signaling, we and others have demonstrated that cross-linking of CD45 with mAbs can induce cell death in T lymphocytes. To investigate the role of CD45 phosphatase activity in apoptosis induction, we expressed either wild-type or phosphatase-dead CD45 molecules in a CD45-deficient BW5147 T cell line. We show here that the phosphatase activity of CD45 was not required for apoptosis triggering after cross-linking of the molecule. It is noteworthy that a revertant of the CD45-negative BW5147 cell line, expressing a truncated form of CD45 lacking most of the cytoplasmic domain, was also susceptible to CD45-mediated death. Moreover, we also demonstrate that leukocyte phosphatase-associated phosphoprotein expression is totally dispensable for CD45-mediated apoptosis to occur. Taken together, these results strongly suggest a role for the extracellular and/or the transmembrane portion of CD45 in apoptosis signaling, which contrasts with the previously reported functions for CD45 in T lymphocytes.
Fortin
Marylène
M
Division of Research and Development, PROCREA BioSciences, Inc., Montréal, Québec, Canada.
Steff
Ann-Muriel
AM
Felberg
Jackie
J
Ding
Isabelle
I
Schraven
Burkhart
B
Johnson
Pauline
P
Hugo
Patrice
P
D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D024201:Bystander Effect / Q000276:immunology; D020169:Caspases / Q000502:physiology; D003545:Cysteine / Q000235:genetics; D003593:Cytoplasm / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D004789:Enzyme Activation / Q000235:genetics / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008863:Microspheres; D010750:Phosphoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary / Q000235:genetics; D017027:Protein Tyrosine Phosphatases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D012694:Serine / Q000235:genetics; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; C513303:Ptprcap protein, mouse; D012694:Serine; D017493:Leukocyte Common Antigens; D017027:Protein Tyrosine Phosphatases; D020169:Caspases; D003545:Cysteine