Linker for activation of T cells (LAT) plays a key role in T-cell antigenic signaling in mammals. Accordingly, LAT orthologues were identified in the majority of vertebrates. However, LAT orthologues were not identified in most birds. In this study, we show that LAT gene is present in genomes of multiple extant birds. It was not properly assembled previously because of its GC-rich content. LAT expression is enriched in lymphoid organs in chicken. The analysis of the coding sequences revealed a strong conservation of key signaling motifs in LAT between chicken and human. Overall, our data indicate that mammalian and avian LAT genes are functional homologues with a common role in T-cell signaling.

• MeSH
• adaptorové proteiny signální transdukční * genetika   MeSH
• fosfoproteiny metabolismus   MeSH
• genom MeSH
• kur domácí genetika   metabolismus   MeSH
• lidé MeSH
• membránové proteiny * genetika   MeSH
• savci genetika   MeSH
• T-lymfocyty metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adaptorové proteiny signální transdukční * MeSH
• fosfoproteiny MeSH
• membránové proteiny * MeSH

Although signal transduction by immunoreceptors such as the T cell antigen receptor (TCR), B cell antigen receptor (BCR), and Fc receptors uses the same schematic and similar molecules, the threshold and the fine-tuning are set differently for each receptor. One manifestation of these differences is that inhibition of Src family kinases (SFK) blocks TCR but not BCR signaling. SFKs are key kinases phosphorylating immunoreceptor tyrosine-based activation motifs (ITAM) in both these receptors. However, it has been proposed that in B cells, downstream kinase SYK can phosphorylate ITAM sequences independently of SFK, allowing it to compensate for the loss of SFK activity, whereas its T cell paralog ZAP-70 is not capable of this compensation. To test this proposal, we examined signaling in SYK- and ZAP-70-deficient B and T cell lines expressing SYK or ZAP-70. We also analyzed signal transduction in T cells expressing BCR or B cells expressing part of the TCR complex. We show that when compared with ZAP-70, SYK lowered the threshold for SFK activity necessary to initiate antigen receptor signaling in both T and B cells. However, neither SYK nor ZAP-70 were able to initiate signaling independently of SFK. We further found that additional important factors are involved in setting this threshold. These include differences between the antigen receptor complexes themselves and the spatial separation of the key transmembrane adaptor protein LAT from the TCR. Thus, immunoreceptor sensing of SFK activity is a complex process regulated at multiple levels.

• Klíčová slova
• B-cell receptor, SYK-family kinases, Src-family kinases, T-cell receptor (TCR), adaptor protein, calcium, inhibitor, receptor regulation, signal transduction, tyrosine-protein kinase (tyrosine kinase),
• MeSH
• B-lymfocyty metabolismus   MeSH
• Jurkat buňky MeSH
• kinasa Syk genetika   metabolismus   MeSH
• lidé MeSH
• protein-tyrosinkináza ZAP-70 genetika   metabolismus   MeSH
• receptory antigenů B-buněk genetika   metabolismus   MeSH
• receptory antigenů T-buněk genetika   metabolismus   MeSH
• signální transdukce * MeSH
• skupina kinas odvozených od src-genu genetika   metabolismus   MeSH
• T-lymfocyty metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• kinasa Syk MeSH
• protein-tyrosinkináza ZAP-70 MeSH
• receptory antigenů B-buněk MeSH
• receptory antigenů T-buněk MeSH
• skupina kinas odvozených od src-genu MeSH
• SYK protein, human MeSH Prohlížeč
• ZAP70 protein, human MeSH Prohlížeč