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Titolo:
Essential role for Gab2 in the allergic response
Autore:
Gu, HH; Saito, K; Klaman, LD; Shen, JQ; Fleming, T; Wang, YP; Pratt, JC; Lin, GS; Lim, B; Kinet, JP; Neel, BG;
Indirizzi:
Beth Israel Deaconess Med Ctr, Div Hematol & Oncol, Canc Biol Program, Boston, MA 02215 USA Beth Israel Deaconess Med Ctr Boston MA USA 02215 m, Boston, MA 02215 USA Beth Israel Deaconess Med Ctr, Dept Med, Div Expt Pathol, Boston, MA 02215USA Beth Israel Deaconess Med Ctr Boston MA USA 02215 ol, Boston, MA 02215USA Harvard Univ, Sch Med, Boston, MA 02215 USA Harvard Univ Boston MA USA 02215 vard Univ, Sch Med, Boston, MA 02215 USA Franklin W Olin Coll Engn, Needham, MA 02492 USA Franklin W Olin Coll Engn Needham MA USA 02492 ngn, Needham, MA 02492 USA
Titolo Testata:
NATURE
fascicolo: 6843, volume: 412, anno: 2001,
pagine: 186 - 190
SICI:
0028-0836(20010712)412:6843<186:ERFGIT>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
PHOSPHOLIPASE C-GAMMA; MAST-CELL ACTIVATION; FC-EPSILON-RI; PROTEIN-KINASE ACTIVATION; GROWTH-FACTOR RECEPTORS; PHOSPHATIDYLINOSITOL 3-KINASE; SIGNAL-TRANSDUCTION; ANTIGEN RECEPTORS; T-CELL; CYTOKINE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Agriculture,Biology & Environmental Sciences
Life Sciences
Physical, Chemical & Earth Sciences
Citazioni:
29
Recensione:
Indirizzi per estratti:
Indirizzo: Gu, HH Beth Israel Deaconess Med Ctr, Div Hematol & Oncol, Canc Biol Program, Boston, MA 02215 USA Beth Israel Deaconess Med Ctr Boston MA USA 02215on, MA 02215 USA
Citazione:
H.H. Gu et al., "Essential role for Gab2 in the allergic response", NATURE, 412(6843), 2001, pp. 186-190

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(1). Mice lacking Gab1 die during embryogenesis and show defective responses to several stimuli(2,3). 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 FceRI 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.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 01:35:38