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 Immunoljournal_title
Nature immunologyauthors
Tam SY,Tsai M,Snouwaert JN,Kalesnikoff J,Scherrer D,Nakae S,Chatterjea D,Bouley DM,Galli SJdoi
10.1038/ni1093keywords:
subject
Has Abstractpub_date
2004-08-01 00:00:00pages
844-52issue
8eissn
1529-2908issn
1529-2916pii
ni1093journal_volume
5pub_type
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