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.
Non–T Cell Activation Linker (NTAL) : A Transmembrane Adaptor Protein Involved in Immunoreceptor Signaling
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Tomáš Brdička, Martin Imrich, Pavla Angelisová, Naděžda Brdičková, Ondrej Horváth, Jiří Špička, Ivan Hilgert, Petra Lusková, Petr Dráber, Petr Novák, Niklas Engels, Jürgen Wienands, Luca Simeoni, Jan Österreicher, Enrique Aguado, Marie Malissen, Burkhart Schraven, Václav Hořejší; Non–T Cell Activation Linker (NTAL) : A Transmembrane Adaptor Protein Involved in Immunoreceptor Signaling . J Exp Med 16 December 2002; 196 (12): 1617–1626. doi: https://doi.org/10.1084/jem.20021405
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