title: Recruitment of SHP-1 protein tyrosine phosphatase and signalling by a chimeric T-cell receptor-killer inhibitory receptor.
abstract: Receptors expressing the immunoreceptor tyrosine-based inhibitory motif (ITIM) in their cytoplasmic tail play an important role in the negative regulation of natural killer and B-cell activation. A subpopulation of T cells expresses the ITIM containing killer cell inhibitory receptor (KIR), which recognize MHC class I molecules. Following coligation of KIR with an activating receptor, the tyrosine in the ITIM is phosphorylated and the cytoplasmic protein tyrosine phosphatase SHP-1 is recruited to the ITIM via its SH2 domains. It is still not clear how SHP-1 affects T-cell receptor (TCR) signalling. In this study, we constructed a chimeric TCR-KIR receptor. We demonstrated that SHP-1 is recruited to the chimeric TCR-KIR receptor following T-cell stimulation with either anti-TCR monoclonal antibody (MoAb) or superantigen. However, in spite of this we could not detect any effect of SHP-1 on TCR signalling regarding total protein tyrosine phosphorylation, TCR down-regulation, mobilization of intracellular free calcium, or induction of the activation markers CD69 and CD25.
authors.affiliation: Institute of Medical Microbiology and Immunology, University of Copenhagen, Denmark.
authors.forename: M D
authors.initials: MD
authors.lastname: Christensen
authors.forename: C
authors.initials: C
authors.lastname: Geisler
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D017252:CD3 Complex / Q000096:biosynthesis / Q000235:genetics; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D007694:Killer Cells, Natural / Q000378:metabolism*; D037181:Lectins, C-Type; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism* / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis / Q000235:genetics; D011971:Receptors, Immunologic / Q000235:genetics / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D054340:Receptors, KIR; D011993:Recombinant Fusion Proteins / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*; D014443:Tyrosine / Q000378:metabolism; D000097682:Lamin B Receptor; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D002118:Calcium; D047908:Intracellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D008024:Ligands; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; D011948:Receptors, Antigen, T-Cell; D018160:Receptors, Cytoplasmic and Nuclear; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D054340:Receptors, KIR; D011993:Recombinant Fusion Proteins; D014443:Tyrosine; D000097682:Lamin B Receptor; D000099192:CD69 Antigens; C509249:PTPN6 protein, human; C509248:Ptpn6 protein, mouse