Abstract

Mast cells play an important role in many inflammatory and immunological reactions by releasing an array of mediators. The goal of our studies is to understand the intracellular signal transduction pathways that lead to the release of these molecules. In previous studies we observed that protein tyrosine phosphorylation is an early and critical signal for FceRI induced degranulation. The protein tyrosine kinase Syk was found to be tyrosine phosphorylated and activated after receptor aggregation. Syk was also shown to be essential for the receptor-induced release of inflammatory mediators. Recent studies demonstrated that the linker region of Syk plays an important role in regulating its function. Studies also defined the mechanisms for the down regulation of signaling in cells by several mechanisms including the degradation of proteins that are activated and by interaction of regulatory and signaling molecules.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Intramural Research (Z01)
Project #
1Z01DE000696-05
Application #
6814542
Study Section
(OIIB)
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2003
Total Cost
Indirect Cost

  Institution

Name
Dental & Craniofacial Research
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Oliver, Constance; Fujimura, Akira; Silveira E Souza, Adriana Maria Mariano et al. (2007) Mast cell-specific gangliosides and FcepsilonRI follow the same endocytic pathway from lipid rafts in RBL-2H3 cells. J Histochem Cytochem 55:315-25
Ganguly, Surajit; Grodzki, Cristina; Sugden, David et al. (2007) Neural adrenergic/cyclic AMP regulation of the immunoglobulin E receptor alpha-subunit expression in the mammalian pinealocyte: a neuroendocrine/immune response link? J Biol Chem 282:32758-64
Zhang, Juan; Suzuki, Katsuhiro; Hitomi, Tomohiro et al. (2007) TOM1L1 is a Lyn substrate involved in FcepsilonRI signaling in mast cells. J Biol Chem 282:37669-77
Song, Haifeng; Zhang, Juan; Chiang, Y Jeffrey et al. (2007) Redundancy in B cell developmental pathways: c-Cbl inactivation rescues early B cell development through a B cell linker protein-independent pathway. J Immunol 178:926-35
Mazzoni, Alessandra; Siraganian, Reuben P; Leifer, Cynthia A et al. (2006) Dendritic cell modulation by mast cells controls the Th1/Th2 balance in responding T cells. J Immunol 177:3577-81
Zudaire, Enrique; Martinez, Alfredo; Garayoa, Mercedes et al. (2006) Adrenomedullin is a cross-talk molecule that regulates tumor and mast cell function during human carcinogenesis. Am J Pathol 168:280-91
Jamur, Maria Celia; Grodzki, Ana Cristina G; Berenstein, Elsa H et al. (2005) Identification and characterization of undifferentiated mast cells in mouse bone marrow. Blood 105:4282-9
Suzuki-Inoue, Katsue; Wilde, Jonathan I; Andrews, Robert K et al. (2004) Glycoproteins VI and Ib-IX-V stimulate tyrosine phosphorylation of tyrosine kinase Syk and phospholipase Cgamma2 at distinct sites. Biochem J 378:1023-9
Hitomi, Tomohiro; Zhang, Juan; Nicoletti, Liliana M et al. (2004) Phospholipase D1 regulates high-affinity IgE receptor-induced mast cell degranulation. Blood 104:4122-8
Zhang, Juan; Chiang, Yungping J; Hodes, Richard J et al. (2004) Inactivation of c-Cbl or Cbl-b differentially affects signaling from the high affinity IgE receptor. J Immunol 173:1811-8

Showing the most recent 10 out of 27 publications