CD45 ectodomain controls interaction with GEMs and Lck activity for optimal TCR signaling.
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.
Irles
Claudine
C
Molecular Immunology Unit, Department of Immunology, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris Cedex 15, France.
Symons
Antony
A
Michel
Frédérique
F
Bakker
Talitha R
TR
van der Merwe
P Anton
PA
Acuto
Oreste
O
D000818:Animals; D015703:Antigens, CD; D018801:CD2 Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D019281:Dimerization; D006028:Glycosphingolipids / Q000378:metabolism*; D006801:Humans; D017493:Leukocyte Common Antigens / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051917:Leukosialin; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism*; D008563:Membrane Lipids / Q000378:metabolism*; D051379:Mice; D017434:Protein Structure, Tertiary; D051381:Rats; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012795:Sialoglycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018800:Thy-1 Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D015703:Antigens, CD; D018801:CD2 Antigens; D006028:Glycosphingolipids; D051917:Leukosialin; D008563:Membrane Lipids; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; C465014:SPN protein, human; D012795:Sialoglycoproteins; C497863:Spn protein, mouse; C497864:Spn protein, rat; D018800:Thy-1 Antigens; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D017493:Leukocyte Common Antigens