Journal of Leukocyte Biology
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Originally published online as doi:10.1189/jlb.0304179 on July 7, 2004

Published online before print July 7, 2004
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(Journal of Leukocyte Biology. 2004;76:896-903.)
© 2004 by Society for Leukocyte Biology

The absence of Grb2-associated binder 2 (Gab2) does not disrupt NK cell development and functions

Simona Zompi*, Hahiua Gu{dagger} and Francesco Colucci*,1

* Cytokines and Lymphoid Development Unit, Department of Immunology, The Pasteur Institute, Paris, France; and
{dagger} Cancer Biology Program, Beth Israel-Deaconess Medical Center, Boston, Massachusetts

1Correspondence: Department of Immunology, Institut Pasteur, 25-28 rue Dr Roux, 75015 Paris, France. E-mail: cecco{at}pasteur.fr

Scaffolding molecules bind simultaneously and link together various components of signal-transduction pathways. Grb2-associated binder 2 (Gab2) is a scaffolding protein required for Fc{gamma}R-initiated allergic responses in mast cells and Fc{gamma}R-mediated phagocytosis in macrophages, where it links IgE and IgG receptors to the phosphatidylinositol-3 kinase (PI-3K) pathway. The Fc{gamma}R expressed by natural killer (NK) cells triggers antibody-dependent cellular cytotoxicity (ADCC). We show here that mouse NK cells express Gab2 and that although PI-3K was required for ADCC, this Fc{gamma}R-mediated function was normal in Gab2–/– NK cells. Moreover, NK cell development, spontaneous cytotoxicity, and responses to and production of cytokines were not perturbed in Gab2–/– mice. Considering the striking differences between the signaling requirements of Fc{gamma}R in macrophages and NK cells, our findings suggest that the organization of signal transduction downstream of the same FcR can be cell type-specific. Conversely, Gab family members Gab1, Gab2, and Gab3 may play specific roles in different leukocytes. As pharmacological targeting of Gab2 in mast cells is a potential strategy to treat allergy, our results suggest prudence, as NK cells may participate in IgE-mediated anaphylaxis in a Gab2-independent manner.

Key Words: cell-mediated cytotoxicity • intracellular signaling • FcR functions




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