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The Journal of Immunology, 2002, 168: 6084-6089.
Copyright © 2002 by The American Association of Immunologists

Apoptosis Mediated Through CD45 Is Independent of Its Phosphatase Activity and Association with Leukocyte Phosphatase-Associated Phosphoprotein1

Marylène Fortin*, Ann-Muriel Steff*, Jackie Felberg{dagger}, Isabelle Ding{ddagger}, Burkhart Schraven{ddagger}, Pauline Johnson{dagger} and Patrice Hugo2,*

* Division of Research and Development, PROCREA BioSciences, Inc., Montréal, Québec, Canada; {dagger} Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada; and {ddagger} Otto von Guericke Universität Magdeburg, Institute of Immunology, Magdeburg, Germany

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.




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