Essential role for Gab2 in the allergic response View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2001-07

AUTHORS

Haihua Gu, Kan Saito, Lori D. Klaman, Junqing Shen, Tony Fleming, YongPing Wang, Joanne C. Pratt, Guosheng Lin, Bing Lim, Jean-Pierre Kinet, Benjamin G. Neel

ABSTRACT

Dos/Gab family scaffolding adapters (Dos, Gab1, Gab2) bind several signal relay molecules, including the protein-tyrosine phosphatase Shp-2 and phosphatidylinositol-3-OH kinase (PI(3)K); they are also implicated in growth factor, cytokine and antigen receptor signal transduction. Mice lacking Gab1 die during embryogenesis and show defective responses to several stimuli. Here we report that Gab2-/- mice are viable and generally healthy; however, the response (for example, degranulation and cytokine gene expression) of Gab2-/- mast cells to stimulation of the high affinity immunoglobulin-epsilon (IgE) receptor Fc(epsilon)RI is defective. Accordingly, allergic reactions such as passive cutaneous and systemic anaphylaxis are markedly impaired in Gab2-/- mice. Biochemical analyses reveal that signalling pathways dependent on PI(3)K, a critical component of Fc(epsilon)RI signalling, are defective in Gab2-/- mast cells. Our data identify Gab2 as the principal activator of PI(3)K in response to Fc(epsilon)RI activation, thereby providing genetic evidence that Dos/Gab family scaffolds regulate the PI(3)K pathway in vivo. Gab2 and/or its associated signalling molecules may be new targets for developing drugs to treat allergy. More... »

PAGES

186

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/35084076

DOI

http://dx.doi.org/10.1038/35084076

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1001358984

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/11449275


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