CD45 ectodomain controls interaction with GEMs and Lck activity for optimal TCR signaling

Claudine Irles; Antony Symons; Frédérique Michel; Talitha R Bakker; P Anton van der Merwe; Oreste Acuto

doi:10.1038/ni877

CD45 ectodomain controls interaction with GEMs and Lck activity for optimal TCR signaling

Nat Immunol. 2003 Feb;4(2):189-97. doi: 10.1038/ni877. Epub 2002 Dec 23.

Authors

Claudine Irles¹, Antony Symons, Frédérique Michel, Talitha R Bakker, P Anton van der Merwe, Oreste Acuto

Affiliation

¹ Molecular Immunology Unit, Department of Immunology, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris Cedex 15, France.

PMID: 12496963
DOI: 10.1038/ni877

Abstract

The transmembrane phosphatase CD45 regulates both Lck activity and T cell receptor (TCR) signaling. Here we have tested whether the large ectodomain of CD45 has a role in this regulation. A CD45 chimera containing the large ectodomain of CD43 efficiently rescues TCR signaling in CD45-null T cells, whereas CD45 chimeras containing small ectodomains from other phosphatases do not. Both basal Lck activity in unstimulated cells and the TCR-induced increase in tyrosine phosphorylation of the TCR zeta-chain and in Lck activity depend on the expression of CD45 with a large ectodomain. Unlike CD45 chimeras containing small ectodomains, both the CD45 chimera with a large ectodomain and wild-type CD45 itself are partially localized to glycosphingolipid-enriched membranes (GEMs). Taken together, these data show that the large CD45 ectodomain is required for optimal TCR signaling.

Publication types

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

MeSH terms

Animals
Antigens, CD*
CD2 Antigens / chemistry
CD2 Antigens / genetics
CD2 Antigens / metabolism
Cell Line
Dimerization
Glycosphingolipids / metabolism*
Humans
Leukocyte Common Antigens / chemistry*
Leukocyte Common Antigens / genetics
Leukocyte Common Antigens / metabolism*
Leukosialin
Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / metabolism*
Membrane Lipids / metabolism*
Mice
Protein Structure, Tertiary
Rats
Receptors, Antigen, T-Cell / metabolism*
Recombinant Fusion Proteins / chemistry
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / metabolism
Sialoglycoproteins / chemistry
Sialoglycoproteins / genetics
Sialoglycoproteins / metabolism
Signal Transduction
T-Lymphocytes / immunology
T-Lymphocytes / metabolism
Thy-1 Antigens / chemistry
Thy-1 Antigens / genetics
Thy-1 Antigens / metabolism
Transfection

Substances

Antigens, CD
CD2 Antigens
Glycosphingolipids
Leukosialin
Membrane Lipids
Receptors, Antigen, T-Cell
Recombinant Fusion Proteins
SPN protein, human
Sialoglycoproteins
Spn protein, mouse
Spn protein, rat
Thy-1 Antigens
Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
Leukocyte Common Antigens