NDLI: Critical role for scaffolding adapter Gab2 in FcγR-mediated phagocytosis

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Critical role for scaffolding adapter Gab2 in FcγR-mediated phagocytosis

Content Provider	Semantic Scholar
Author	Gu, Haihua Botelho, Roberto J. Yu, Min Grinstein, Sergio Neel, Benjamin G.
Copyright Year	2003
Abstract	Grb2-associated binder 2 (Gab2), a member of the Dos/Gab subfamily scaffolding molecules, plays important roles in regulating the growth, differentiation, and function of many hematopoietic cell types. In this paper, we reveal a novel function of Gab2 in Fcgamma receptor (FcgammaR)-initiated phagocytosis in macrophages. Upon FcgammaR activation, Gab2 becomes tyrosyl phosphorylated and associated with p85, the regulatory subunit of phosphoinositide 3-kinase (PI3K), and the protein-tyrosine phosphatidylinositol Shp-2. FcgammaR-mediated phagocytosis is severely impaired in bone marrow-derived macrophages from Gab2-/- mice. The defect in phagocytosis correlates with decreased FcgammaR-evoked activation of Akt, a downstream target of PI3K. Using confocal fluorescence microscopy, we find that Gab2 is recruited to the nascent phagosome, where de novo PI3K lipid production occurs. Gab2 recruitment requires the pleckstrin homology domain of Gab2 and is sensitive to treatment with the PI3K inhibitor wortmannin. The Grb2 binding site on Gab2 also plays an auxiliary role in recruitment to the phagosome. Because PI3K activity is required for FcgammaR-mediated phagocytosis, our results indicate that Gab2 acts as a key component of FcgammaR-mediated phagocytosis, most likely by amplifying PI3K signaling in the nascent phagosome.
Starting Page	1151
Ending Page	1161
Page Count	11
File Format	PDF HTM / HTML
PubMed reference number	12821647
Volume Number	161
Journal	The Journal of cell biology
Alternate Webpage(s)	https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e7/7f/200212158.PMC2172986.pdf
Alternate Webpage(s)	http://jcb.rupress.org/content/jcb/161/6/1151.full.pdf
Language	English
Access Restriction	Open
Subject Keyword	1-Phosphatidylinositol 3-Kinase Binder, device Bone Marrow Homologous Gene Maxillonasal dysplasia, Binder type Microscopy, Fluorescence Phagocytosis Phagosomes Phosphatidylinositols Pleckstrin Homology Domains Proto-Oncogene Proteins c-akt Receptors, IgG Subfamily Tyrosine cell type macrophage wortmannin
Content Type	Text
Resource Type	Article

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