LAT is essential for FcεRI-mediated mast cell activation

被引：313

作者：

Saitoh, S

Arudchandran, R

Manetz, TS

Zhang, WG

Sommers, CL

Love, PE

Rivera, J

Samelson, LE

机构：

[1] NCI, Cellular & Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA

[2] NIAMSD, Sect Chem Immunol, NIH, Bethesda, MD 20892 USA

[3] NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA

来源：

IMMUNITY | 2000年 / 12卷 / 05期

基金：

日本学术振兴会;

关键词：

D O I：

10.1016/S1074-7613(00)80204-6

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The linker molecule LAT is a substrate of the tyrosine kinases activated following TCR engagement of T cells. LAT is also expressed in platelets, NK, and mast cells. Although LAT-deficient mice contain normal numbers of mast cells, we found that LAT-deficient mice were resistant to IgE-mediated passive systemic anaphylaxis. LAT-deficient bone marrow-derived mast cells (BMMC) showed normal growth and development. Whereas tyrosine phosphorylation of Fc epsilon RI, Syk, and Vav was intact in LAT-deficient BMMCs following Fc epsilon RI engagement, tyrosine phosphorylation of SLP-76, PLC-gamma 1, and PLC-gamma 2 and calcium mobilization were dramatically reduced. LAT-deficient BMMCs also exhibited profound defects in activation of MAPK, degranulation, and cytokine production after Fc epsilon RI cross-linking. These results show that LAT plays a critical role in Fc epsilon RI-mediated signaling in mast cells.

引用

页码：525 / 535

页数：11

共 53 条

[1]

ALBER G, 1991, J BIOL CHEM, V266, P22613

[2] The Src homology 2 domain of Vav is required for its compartmentation to the plasma membrane and activation of C-jun NH2-terminal kinase 1 [J].