Differential requirements for Vav proteins in DAP10- and ITAM-mediated NK cell cytotoxicity

Marina Cella, Keiko Fujikawa, Ilaria Tassi, Sunjin Kim, Kevin Latinis, Shinzo Nishi, Wayne Yokoyama, Marco Colonna, Wojciech Swat

Research output: Contribution to journalArticlepeer-review

87 Scopus citations

Abstract

Natural killer (NK) cells express multiple activating receptors that initiate signaling cascades through DAP10- or immunoreceptor tyrosine-based activation motif-containing adapters, including DAP12 and FcRγ. Among downstream signaling mediators, the guanine nucleotide exchange factor Vav1 carries out a key role in activation. However, whether Vavl regulates only some or all NK cell-activating pathways is matter of debate. It is also possible that two other Vav family molecules, Vav2 and Vav3, are involved in NK cell activation. Here, we examine the relative contribution of each of these exchange factors to NK cell-mediated cytotoxicity using mice lacking one, two, or all three Vav proteins. We found that Vav1 deficiency is sufficient to disrupt DAP10-mediated cytotoxicity, whereas lack of Vav2 and Vav3 profoundly impairs FcRγ- and DAP12-mediated cytotoxicity. Our results provide evidence that these three Vav proteins function specifically in distinct pathways that trigger NK cell cytotoxicity.

Original languageEnglish
Pages (from-to)817-823
Number of pages7
JournalJournal of Experimental Medicine
Volume200
Issue number6
DOIs
StatePublished - Sep 20 2004

Keywords

  • Adapters
  • DAP12
  • FcRγ
  • GEF
  • NKG2D

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