1. Non–T Cell Activation Linker (NTAL)
- Author
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Tomas Brdicka, Petra Lusková, Marie Malissen, Jürgen Wienands, Luca Simeoni, Enrique Aguado, Ivan Hilgert, Jiri Spicka, Ondrej Horvath, Petr Novák, Naděžda Brdičková, Vaclav Horejsi, Petr Dráber, Burkhart Schraven, Pavla Angelisova, Martin Imrich, Niklas Engels, and Jan Österreicher
- Subjects
0303 health sciences ,biology ,CD3 ,T cell ,Immunology ,T-cell receptor ,B-cell receptor ,Linker for Activation of T cells ,Signal transducing adaptor protein ,Molecular biology ,Cell biology ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,biology.protein ,medicine ,Immunology and Allergy ,GRB2 ,Cell activation ,030304 developmental biology ,030215 immunology - Abstract
A key molecule necessary for activation of T lymphocytes through their antigen-specific T cell receptor (TCR) is the transmembrane adaptor protein LAT (linker for activation of T cells). Upon TCR engagement, LAT becomes rapidly tyrosine phosphorylated and then serves as a scaffold organizing a multicomponent complex that is indispensable for induction of further downstream steps of the signaling cascade. Here we describe the identification and preliminary characterization of a novel transmembrane adaptor protein that is structurally and evolutionarily related to LAT and is expressed in B lymphocytes, natural killer (NK) cells, monocytes, and mast cells but not in resting T lymphocytes. This novel transmembrane adaptor protein, termed NTAL (non–T cell activation linker) is the product of a previously identified WBSCR5 gene of so far unknown function. NTAL becomes rapidly tyrosine-phosphorylated upon cross-linking of the B cell receptor (BCR) or of high-affinity Fcγ- and Fcε-receptors of myeloid cells and then associates with the cytoplasmic signaling molecules Grb2, Sos1, Gab1, and c-Cbl. NTAL expressed in the LAT-deficient T cell line J.CaM2.5 becomes tyrosine phosphorylated and rescues activation of Erk1/2 and minimal transient elevation of cytoplasmic calcium level upon TCR/CD3 cross-linking. Thus, NTAL appears to be a structural and possibly also functional homologue of LAT in non–T cells.
- Published
- 2002