Tyrosine phosphorylation of the linker for activator of T cells in mast cells by stimulation with the high affinity IgE receptor.
Aggregation of the high affinity IgE receptors (FcepsilonRI) on basophils and mast cells, members of the immune receptor family, initiates a cascade of events that results in the release of inflammatory mediators. This pathway involves the activation of several protein-tyrosine kinases, including Lyn, Syk, Btk, and Fak that induce the tyrosine phosphorylation of various proteins. The linker for activation of T cells (LAT), was originally found as a ZAP-70 tyrosine kinase substrate that linked T cell receptors to cellular activation, and was expressed in T cells, NK cells and mast cells. Here we show that LAT expressed in the RBL-2H3 rat mast cell line is tyrosine-phosphorylated after aggregation of FcepsilonRI. The tyrosine phosphorylation of the LAT was dramatically enhanced after receptor aggregation. Furthermore, a tyrosine-phosphorylated 80-kDa protein associated with LAT transiently after receptor aggregation. GST fusion proteins containing parts of PLCgamma or PI3 kinase can bind LAT. These results suggest that LAT plays an important role not only in T cell, but also in mast cell activation, and that the association among these signaling molecules is critical for FcepsilonRI-mediated intracellular signal transduction in mast cells.
Kimura
T
T
The First Department of Internal Medicine, School of Medicine, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, 142-8666, Tokyo, Japan. tkimura-shw@umin.ac.jp
Hisano
M
M
Inoue
Y
Y
Adachi
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D007527:Isoenzymes / Q000378:metabolism; D008213:Lymphocyte Activation; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051966:Phospholipase C gamma; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017455:Receptors, IgE / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D010738:Type C Phospholipases / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D007527:Isoenzymes; D010750:Phosphoproteins; D017455:Receptors, IgE; D014443:Tyrosine; D019869:Phosphatidylinositol 3-Kinases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma