Non-T cell activation linker (NTAL): a transmembrane adaptor protein involved in immunoreceptor signaling.
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 Fcgamma- and Fc epsilon -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.
Brdicka
Tomás
T
Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Vídenská 1083, 142 20 Prague 4, Czech Republic.
Imrich
Martin
M
Angelisová
Pavla
P
Brdicková
Nadezda
N
Horváth
Ondrej
O
Spicka
Jirí
J
Hilgert
Ivan
I
Lusková
Petra
P
Dráber
Petr
P
Novák
Petr
P
Engels
Niklas
N
Wienands
Jürgen
J
Simeoni
Luca
L
Osterreicher
Jan
J
Aguado
Enrique
E
Malissen
Marie
M
Schraven
Burkhart
B
Horejsí
Václav
V
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008221:Lymphoid Tissue / Q000166:cytology / Q000378:metabolism; D021962:Membrane Microdomains / Q000737:chemistry / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D010766:Phosphorylation; D011506:Proteins; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D011961:Receptors, Fc / Q000378:metabolism*; D017455:Receptors, IgE / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C110810:LAT protein, human; C419196:LAT2 protein, human; C488163:LAT2 protein, mouse; C491734:Lat protein, mouse; D008565:Membrane Proteins; D010750:Phosphoproteins; D011506:Proteins; D011947:Receptors, Antigen, B-Cell; D011961:Receptors, Fc; D017455:Receptors, IgE; D017452:Receptors, IgG