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

First Author  Tam SY Year  2004
Journal  Nat Immunol Volume  5
Issue  8 Pages  844-52
PubMed ID  15235600 Mgi Jnum  J:91790
Mgi Id  MGI:3050742 Doi  10.1038/ni1093
Citation  Tam SY, et al. (2004) RabGEF1 is a negative regulator of mast cell activation and skin inflammation. Nat Immunol 5(8):844-52
abstractText  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.
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