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The role of Ras guanine nucleotide releasing protein 4 in Fc epsilonRI-mediated signaling, mast cell function, and T cell development.

Publication ,  Journal Article
Zhu, M; Fuller, DM; Zhang, W
Published in: J Biol Chem
March 9, 2012

The RasGRP (Ras guanine nucleotide-releasing protein) family proteins are guanine nucleotide exchange factors that activate Ras GTPases, ultimately leading to MAPK activation and many cellular processes. The RasGRP family has four members. Published studies demonstrate that RasGRP1, RasGRP2, and RasGRP3 play critical roles in T cells, platelets, and B cells, respectively. RasGRP4 is highly expressed in mast cells. Although previous data suggest that it is important in mast cell development and function, the role of RasGRP4 in mast cells and allergic responses has not been clearly demonstrated. In this study, we generated RasGRP4(-/-) mice to examine the function of RasGRP4. Analyses of these mice showed that mast cells were able to develop normally in vivo and in vitro. Despite high levels of RasGRP4 expression in mast cells, RasGRP4 deficiency led to only a modest reduction in FcεRI-mediated degranulation and cytokine production. Interestingly, mast cells deficient in both RasGRP1 and RasGRP4 had a much more severe block in FcεRI-mediated signaling and mast cell function. We also made the unexpected finding that RasGRP4 functions during thymocyte development. Our data suggest that after the engagement of immunoreceptors, immune cells likely employ multiple members of the RasGRP family to transduce critical signals.

Duke Scholars

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Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

March 9, 2012

Volume

287

Issue

11

Start / End Page

8135 / 8143

Location

United States

Related Subject Headings

  • ras Guanine Nucleotide Exchange Factors
  • Thymocytes
  • T-Lymphocytes
  • Signal Transduction
  • Receptors, IgE
  • Mice, Knockout
  • Mice
  • Mast Cells
  • Hypersensitivity
  • Guanine Nucleotide Exchange Factors
 

Citation

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Zhu, M., Fuller, D. M., & Zhang, W. (2012). The role of Ras guanine nucleotide releasing protein 4 in Fc epsilonRI-mediated signaling, mast cell function, and T cell development. J Biol Chem, 287(11), 8135–8143. https://doi.org/10.1074/jbc.M111.320580
Zhu, Minghua, Deirdre M. Fuller, and Weiguo Zhang. “The role of Ras guanine nucleotide releasing protein 4 in Fc epsilonRI-mediated signaling, mast cell function, and T cell development.J Biol Chem 287, no. 11 (March 9, 2012): 8135–43. https://doi.org/10.1074/jbc.M111.320580.
Zhu, Minghua, et al. “The role of Ras guanine nucleotide releasing protein 4 in Fc epsilonRI-mediated signaling, mast cell function, and T cell development.J Biol Chem, vol. 287, no. 11, Mar. 2012, pp. 8135–43. Pubmed, doi:10.1074/jbc.M111.320580.

Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

March 9, 2012

Volume

287

Issue

11

Start / End Page

8135 / 8143

Location

United States

Related Subject Headings

  • ras Guanine Nucleotide Exchange Factors
  • Thymocytes
  • T-Lymphocytes
  • Signal Transduction
  • Receptors, IgE
  • Mice, Knockout
  • Mice
  • Mast Cells
  • Hypersensitivity
  • Guanine Nucleotide Exchange Factors