Apoptosis mediated through CD45 is independent of its phosphatase activity and association with leukocyte phosphatase-associated phosphoprotein

Marylène Fortin; Ann-Muriel Steff; Jackie Felberg; Isabelle Ding; Burkhart Schraven; Pauline Johnson; Patrice Hugo

doi:10.4049/jimmunol.168.12.6084

Apoptosis mediated through CD45 is independent of its phosphatase activity and association with leukocyte phosphatase-associated phosphoprotein

J Immunol. 2002 Jun 15;168(12):6084-9. doi: 10.4049/jimmunol.168.12.6084.

Authors

Marylène Fortin¹, Ann-Muriel Steff, Jackie Felberg, Isabelle Ding, Burkhart Schraven, Pauline Johnson, Patrice Hugo

Affiliation

¹ Division of Research and Development, PROCREA BioSciences, Inc., Montréal, Québec, Canada.

PMID: 12055218
DOI: 10.4049/jimmunol.168.12.6084

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Substitution / genetics
Animals
Antibodies, Monoclonal / metabolism
Apoptosis / genetics
Apoptosis / immunology*
Bystander Effect / immunology
Caspases / physiology
Cysteine / genetics
Cytoplasm / enzymology
Cytoplasm / genetics
Cytoplasm / immunology
Enzyme Activation / genetics
Enzyme Activation / immunology
Intracellular Signaling Peptides and Proteins
Leukocyte Common Antigens / genetics
Leukocyte Common Antigens / immunology
Leukocyte Common Antigens / metabolism
Leukocyte Common Antigens / physiology*
Membrane Proteins
Mice
Mice, Inbred C57BL
Mice, Knockout
Microspheres
Phosphoproteins / deficiency
Phosphoproteins / genetics
Phosphoproteins / metabolism*
Precipitin Tests
Protein Structure, Tertiary / genetics
Protein Tyrosine Phosphatases / deficiency
Protein Tyrosine Phosphatases / genetics
Protein Tyrosine Phosphatases / metabolism*
Protein Tyrosine Phosphatases / physiology
Serine / genetics
T-Lymphocytes / cytology
T-Lymphocytes / enzymology
T-Lymphocytes / immunology
Thymus Gland / cytology
Thymus Gland / enzymology
Thymus Gland / immunology
Transfection
Tumor Cells, Cultured

Substances

Antibodies, Monoclonal
Intracellular Signaling Peptides and Proteins
Membrane Proteins
Phosphoproteins
Ptprcap protein, mouse
Serine
Leukocyte Common Antigens
Protein Tyrosine Phosphatases
Caspases
Cysteine