Differential requirements for CD45 in NK-cell function reveal distinct roles for Syk-family kinases.
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.
Department of Microbiology and Immunology and the Cancer Research Institute, USA.
David G T
DG
Hesslein
Emil H
EH
Palacios
Joseph C
JC
Sun
Joshua N
JN
Beilke
Susan R
SR
Watson
Arthur
A
Weiss
Lewis L
LL
Lanier
D020816:Amino Acid Motifs; D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D015550:Cell Degranulation / Q000276:immunology; D049109:Cell Proliferation; D006566:Herpesviridae Infections / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D007371:Interferon-gamma / Q000096:biosynthesis; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000201:enzymology* / Q000276:immunology* / Q000502:physiology; D017493:Leukocyte Common Antigens / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D018146:Muromegalovirus / Q000502:physiology; D055650:NK Cell Lectin-Like Receptor Subfamily A / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism; D000072377:Syk Kinase; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism
D047908:Intracellular Signaling Peptides and Proteins; C527096:Klra8 protein, mouse; D055650:NK Cell Lectin-Like Receptor Subfamily A; D011991:Receptors, Virus; D007371:Interferon-gamma; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D051746:ZAP-70 Protein-Tyrosine Kinase; C497262:Zap70 protein, mouse; D017493:Leukocyte Common Antigens
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