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

Journal of Leukocyte Biology
Simona ZompiFrancesco Colucci

Abstract

Scaffolding molecules bind simultaneously and link together various components of signal-transduction pathways. Grb2-associated binder 2 (Gab2) is a scaffolding protein required for FcgammaR-initiated allergic responses in mast cells and FcgammaR-mediated phagocytosis in macrophages, where it links IgE and IgG receptors to the phosphatidylinositol-3 kinase (PI-3K) pathway. The FcgammaR 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 FcgammaR-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 FcgammaR 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 cel...Continue Reading

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Citations

Sep 10, 2009·Cell Communication and Signaling : CCS·Franziska U WöhrleTilman Brummer
Oct 28, 2008·Cellular Signalling·Máté MausGabriella Sármay
Jan 3, 2009·Biological Psychiatry·M Arfan IkramMonique M B Breteler
Jun 8, 2007·Neuron·Eric M ReimanDietrich A Stephan
Jan 9, 2019·SLAS Technology·Christopher HalburEun Ji Chung
Jan 14, 2016·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Lei WangLifeng Qi

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