The phosphatase domains of CD45 are required for ligand induced T-cell receptor downregulation.
Down-regulation of the T-cell receptor (TCR) plays an important role in modulating T-cell responses, both during T-cell development and in mature T cells. At least two distinct pathways exist for TCR down-regulation: down-regulation following TCR ligation; and down-regulation following activation of protein kinase C (PKC). Ligand-induced TCR down-regulation is dependent on protein tyrosine kinase (PTK) activity and seems to be closely related to T-cell activation. In addition, previous studies have indicated that ligand-induced TCR down-regulation is dependent on the expression of CD45, a transmembrane protein tyrosine phosphatase. The role of the different domains of CD45 in TCR down-regulation was investigated in this study. We found that the phosphatase domains of CD45 are required for efficient ligand-induced TCR down-regulation. In contrast, the extracellular domain of CD45 is dispensable for ligand-mediated TCR down-regulation. Finally, PKC-mediated TCR down-regulation was found to be independent of both the extra-and intracellular domains of CD45.
Kastrup
J
J
Institute of Medical Microbiology and Immunology, University of Copenhagen, The Panum Institute, Copenhagen, Denmark.
Lauritsen
J P
JP
Menné
C
C
Dietrich
J
J
Geisler
C
C
D001665:Binding Sites; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D019169:Jurkat Cells; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D008024:Ligands; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D008024:Ligands; D011948:Receptors, Antigen, T-Cell; D014443:Tyrosine; D011493:Protein Kinase C; D010744:Phosphoric Monoester Hydrolases; D017493:Leukocyte Common Antigens