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Cutting edge: differential segregation of the SRC homology 2-containing protein tyrosine phosphatase-1 within the early NK cell immune synapse distinguishes noncytolytic from cytolytic interactions
Journal article   Peer reviewed

Cutting edge: differential segregation of the SRC homology 2-containing protein tyrosine phosphatase-1 within the early NK cell immune synapse distinguishes noncytolytic from cytolytic interactions

Yatin M Vyas, Hina Maniar and Bo Dupont
The Journal of immunology (1950), Vol.168(7), pp.3150-3154
04/01/2002
DOI: 10.4049/jimmunol.168.7.3150
PMID: 11907066

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Abstract

Inhibitory NK receptors with ligand specificity for MHC class I recruit Src homology 2-containing protein tyrosine phosphatase-1 (SHP-1) phosphatase and prevent autocytotoxicity. Activation of SHP-1 depends upon Src kinase-mediated tyrosine phosphorylation of the cytoplasmic domain of the inhibitory receptor. In this study we demonstrate, by quantitative temporal analysis, that talin, Lck, and SHP-1 are recruited to the synapse within 1 min in both cytolytic and noncytolytic conjugates. Polarization of talin and Lck rapidly disappears in the noncytolytic interactions but persists in cytolytic interactions, where protein kinase C-theta;, Src homology 2 domain-containing leukocyte protein of 76 kDa, and lysosomes are recruited within 5 min. At 1 min SHP-1 clusters in the periphery of the cytolytic synapse, whereas it clusters in the center of the noncytolytic synapse. Lck has multifocal distribution in both synapses consistent with the shared requirement for early tyrosine phosphorylation. Our studies indicate that the spatial location of SHP-1 in the synapse distinguishes noncytolytic from cytolytic interactions within the first minute.
Cell Communication - immunology Cytotoxicity Tests, Immunologic Humans Protein Kinase C-theta Intracellular Signaling Peptides and Proteins Lysosomes - enzymology Protein Tyrosine Phosphatases - metabolism Lymphocyte Specific Protein Tyrosine Kinase p56(lck) - metabolism Phosphoproteins - metabolism Talin - metabolism Killer Cells, Natural - enzymology Protein Transport - immunology Signal Transduction - immunology Adaptor Proteins, Signal Transducing Isoenzymes - metabolism Protein Kinase C - metabolism Killer Cells, Natural - immunology Clone Cells src Homology Domains - immunology Lysosomes - immunology Protein Phosphatase 1 Cell Line, Transformed Protein Tyrosine Phosphatase, Non-Receptor Type 6 Cytotoxicity, Immunologic

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