First Author | Liu Y | Year | 2007 |
Journal | J Exp Med | Volume | 204 |
Issue | 1 | Pages | 93-103 |
PubMed ID | 17190838 | Mgi Jnum | J:125310 |
Mgi Id | MGI:3758152 | Doi | 10.1084/jem.20061598 |
Citation | Liu Y, et al. (2007) An essential role for RasGRP1 in mast cell function and IgE-mediated allergic response. J Exp Med 204(1):93-103 |
abstractText | Cross-linking of the FcepsilonRI activates the phosphatidyl inositol 3 kinase (PI3K) and mitogen-activated protein kinase pathways. Previous studies demonstrate that Ras guanyl nucleotide-releasing protein (RasGRP)1 is essential in T cell receptor-mediated Ras-Erk activation. Here, we report that RasGRP1 plays an important role in FcepsilonRI-mediated PI3K activation and mast cell function. RasGRP1-deficient mice failed to mount anaphylactic allergic reactions. RasGRP1-/- mast cells had markedly reduced degranulation and cytokine production. Although FcepsilonRI-mediated Erk activation was normal, PI3K activation was diminished. Consequently, activation of Akt, PIP3-dependent kinase, and protein kinase C delta was defective. Expression of a constitutively active form of N-Ras could rescue the degranulation defect and Akt activation. We further demonstrated that RasGRP1-/- mast cells were defective in granule translocation, microtubule formation, and RhoA activation. Our results identified RasGRP1 as an essential regulator of mast cell function. |