Abstract
EWS/FLI1-activated transcript 2 (EAT-2)A and EAT-2B are single SH2-domain proteins, which bind to phosphorylated tyrosines of signaling lymphocyte activation molecule family receptors in murine NK cells. While EAT-2 is a positive regulator in human cells, a negative regulatory role was attributed to the adapter in NK cells derived from EAT-2A–deficient 129Sv mice. To evaluate whether the genetic background or the presence of a selection marker in the mutant mice could influence the regulatory mode of these adapters, we generated EAT-2A–, EAT-2B–, and EAT-2A/B–deficient mice using C57BL/6 embryonic stem cells. We found that NK cells from EAT-2A– and EAT-2A/B–deficient mice were unable to kill tumor cells in a CD244- or CD84-dependent manner. Furthermore, EAT-2A/B positively regulate phosphorylation of Vav-1, which is known to be implicated in NK cell killing. Thus, as in humans, the EAT-2 adapters act as positive regulators of signaling lymphocyte activation molecule family receptor-specific NK cell functions in C57BL/6 mice.
Footnotes
The work was supported in part by National Institutes of Health Grants PO1 AI- 065687 (to C.T.) and AI067803 (to J.S.).
The online version of this article contains supplemental material.
Abbreviations used in this paper:
- B6
- C57BL/6
- EAT-2
- EWS/FLI1-activated transcript 2
- ES cell
- embryonic stem cell
- IP
- immunoprecipitation
- LDH
- lactate dehydrogenase
- SAP
- signaling lymphocyte activation molecule-associated protein
- SLAM
- signaling lymphocyte activation molecule
- wt
- wild-type.
- Received June 15, 2010.
- Accepted September 15, 2010.
- Copyright © 2010 by The American Association of Immunologists, Inc.