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The absence of Grb2‐associated binder 2 (Gab2) does not disrupt NK cell development and functions
Author(s) -
Zompi Simona,
Gu Hahiua,
Colucci Francesco
Publication year - 2004
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0304179
Subject(s) - antibody dependent cell mediated cytotoxicity , biology , microbiology and biotechnology , immunology , signal transduction , antibody , monoclonal antibody
Scaffolding molecules bind simultaneously and link together various components of signal‐transduction pathways. Grb2‐associated binder 2 (Gab2) is a scaffolding protein required for FcγR‐initiated allergic responses in mast cells and FcγR‐mediated phagocytosis in macrophages, where it links IgE and IgG receptors to the phosphatidylinositol‐3 kinase (PI‐3K) pathway. The FcγR 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 FcγR‐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 FcγR 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.