RabGEF1 is a negative regulator of mast cell activation and skin inflammation.

Abstract:

:Mast cell activation induced by aggregation of Fc epsilon RI receptors with immunoglobulin E and antigen is mediated through the activation of multiple protein kinase cascades. Here we report that the regulatory protein RabGEF1 bound to Ras and negatively regulated Ras activation and its 'downstream' effector pathways in Fc epsilon RI-dependent mast cell activation. RabGEF1-deficient mast cells showed enhanced degranulation and release of lipid mediators and cytokines in response to Fc epsilon RI aggregation. RabGEF1-deficient mice developed severe skin inflammation and had increased numbers of mast cells. Thus, RabGEF1 is a negative regulator of Fc epsilon RI-dependent mast cell activation, and a lack of RabGEF1 results in the development of skin inflammation in vivo.

journal_name

Nat Immunol

journal_title

Nature immunology

authors

Tam SY,Tsai M,Snouwaert JN,Kalesnikoff J,Scherrer D,Nakae S,Chatterjea D,Bouley DM,Galli SJ

doi

10.1038/ni1093

keywords:

subject

Has Abstract

pub_date

2004-08-01 00:00:00

pages

844-52

issue

8

eissn

1529-2908

issn

1529-2916

pii

ni1093

journal_volume

5

pub_type

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