An essential role for RasGRP1 in mast cell function and IgE-mediated allergic response

Mice, Knockout 0303 health sciences MAP Kinase Signaling System Receptors, IgE Articles Immunoglobulin E In Vitro Techniques Models, Biological Cell Degranulation Enzyme Activation Mice Phosphatidylinositol 3-Kinases 03 medical and health sciences Animals Cytokines Guanine Nucleotide Exchange Factors Mast Cells Anaphylaxis Signal Transduction
DOI: 10.1084/jem.20061598 Publication Date: 2006-12-27T01:23:56Z
ABSTRACT
Cross-linking of the FcεRI activates phosphatidyl inositol 3 kinase (PI3K) and mitogen-activated protein pathways. Previous studies demonstrate that Ras guanyl nucleotide-releasing (RasGRP)1 is essential in T cell receptor–mediated Ras-Erk activation. Here, we report RasGRP1 plays an important role FcεRI-mediated PI3K activation mast function. RasGRP1-deficient mice failed to mount anaphylactic allergic reactions. RasGRP1−/− cells had markedly reduced degranulation cytokine production. Although Erk was normal, diminished. Consequently, Akt, PIP3-dependent kinase, C δ defective. Expression a constitutively active form N-Ras could rescue defect Akt We further demonstrated were defective granule translocation, microtubule formation, RhoA Our results identified as regulator
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