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Publication : Differential requirements for CD45 in NK-cell function reveal distinct roles for Syk-family kinases.

First Author  Hesslein DG Year  2011
Journal  Blood Volume  117
Issue  11 Pages  3087-95
PubMed ID  21245479 Mgi Jnum  J:170515
Mgi Id  MGI:4946595 Doi  10.1182/blood-2010-06-292219
Citation  Hesslein DG, et al. (2011) Differential requirements for CD45 in NK-cell function reveal distinct roles for Syk-family kinases. Blood 117(11):3087-95
abstractText  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 zeta 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.
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