Abstract
The protein tyrosine phosphatase CD45 is an important regulator of Src-family kinase activity. We found that in the absence of CD45, natural killer (NK) cells are defective in protecting the host from mouse cytomegalovirus infection. We show that although CD45 is necessary for all immunoreceptor tyrosine-based activation motif (ITAM)-specific NK-cell functions and processes such as degranulation, cytokine production, and expansion during viral infection, the impact of CD45 deficiency on ITAM signaling differs depending on the downstream function. CD45-deficient NK cells are normal in their response to inflammatory cytokines when administered ex vivo and in the context of viral infection. Syk and ζ chain-associated protein kinase 70 (Zap70) are thought to play redundant roles in transmitting ITAM signals in NK cells. We show that Syk, but not Zap70, controls the remaining CD45-independent, ITAM-specific NK-cell functions, demonstrating a functional difference between these 2 Syk-kinase family members in primary NK cells.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Motifs
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Animals
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Antibody-Dependent Cell Cytotoxicity / immunology
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Cell Degranulation / immunology
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Cell Proliferation
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Herpesviridae Infections / immunology
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Herpesviridae Infections / prevention & control
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Herpesviridae Infections / virology
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Interferon-gamma / biosynthesis
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Intracellular Signaling Peptides and Proteins / deficiency
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Intracellular Signaling Peptides and Proteins / metabolism*
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Killer Cells, Natural / enzymology*
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Killer Cells, Natural / immunology*
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Killer Cells, Natural / physiology
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Leukocyte Common Antigens / deficiency
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Leukocyte Common Antigens / metabolism*
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Mice
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Muromegalovirus / physiology
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NK Cell Lectin-Like Receptor Subfamily A / metabolism
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Protein-Tyrosine Kinases / deficiency
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Protein-Tyrosine Kinases / metabolism*
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Receptors, Virus / metabolism
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Syk Kinase
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ZAP-70 Protein-Tyrosine Kinase / metabolism
Substances
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Intracellular Signaling Peptides and Proteins
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Klra8 protein, mouse
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NK Cell Lectin-Like Receptor Subfamily A
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Receptors, Virus
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Interferon-gamma
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Protein-Tyrosine Kinases
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Syk Kinase
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Syk protein, mouse
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ZAP-70 Protein-Tyrosine Kinase
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Zap70 protein, mouse
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Leukocyte Common Antigens