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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Liu, Y; Zhu, M; Nishida, K; Hirano, T; Zhang, W

Published Date

  • January 22, 2007

Published In

Volume / Issue

  • 204 / 1

Start / End Page

  • 93 - 103

PubMed ID

  • 17190838

Pubmed Central ID

  • 17190838

International Standard Serial Number (ISSN)

  • 0022-1007

Digital Object Identifier (DOI)

  • 10.1084/jem.20061598

Language

  • eng

Conference Location

  • United States