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


Authors: Vyas, Y. M.; Maniar, H.; Dupont, B.
Article Title: 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
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-θ, 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.
Keywords: signal transduction; human cell; quantitative assay; protein interaction; cytotoxicity; intracellular signaling peptides and proteins; protein transport; adaptor proteins, signal transducing; cell line, transformed; phosphoproteins; natural killer cell; killer cells, natural; cytolysis; cytotoxicity, immunologic; protein kinase c; protein tyrosine phosphatase; cell interaction; cell communication; clone cells; polarization; isoenzymes; normal human; lysosomes; major histocompatibility antigen class 1; synapse; cytotoxicity tests, immunologic; protein-tyrosine-phosphatase; lymphocyte specific protein tyrosine kinase p56(lck); talin; humans; human; priority journal; article; shp1 protein tyrosine phosphatase; src homology domain; src homology domains
Journal Title: Journal of Immunology
Volume: 168
Issue: 7
ISSN: 0022-1767
Publisher: The American Association of Immunologists, Inc  
Date Published: 2002-04-01
Start Page: 3150
End Page: 3154
Language: English
PUBMED: 11907066
PROVIDER: scopus
DOI: 10.4049/​jimmunol.168.7.3150
DOI/URL:
Notes: Export Date: 14 November 2014 -- Source: Scopus
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MSK Authors
  1. Hina S Maniar
    8 Maniar
  2. Yatin M Vyas
    25 Vyas
  3. Bo Dupont
    264 Dupont