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

• DOI: 10.1084/jem.20061598
• Publication Date: 2006-12-27T01:23:56Z
• Authors: Yan Liu; Minghua Zhu; Keigo Nishida; Toshio Hirano; Weiguo Zhang
• Keywords: 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

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