Nejvíce citovaný článek - PubMed ID 15081526
Transmembrane adaptor proteins in membrane microdomains: important regulators of immunoreceptor signaling
Transmembrane adaptor proteins (TRAPs) are important organizers and regulators of immunoreceptor-mediated signaling. A bioinformatic search revealed several potential novel TRAPs, including a highly conserved protein, proline rich 7 (PRR7), previously described as a component of the PSD-95/N-methyl-d-aspartate receptor protein complex in postsynaptic densities (PSD) of rat neurons. Our data demonstrate that PRR7 is weakly expressed in other tissues but is readily up-regulated in activated human peripheral blood lymphocytes. Transient overexpression of PRR7 in Jurkat T cell line led to gradual apoptotic death dependent on the WW domain binding motif surrounding Tyr-166 in the intracellular part of PRR7. To circumvent the pro-apoptotic effect of PRR7, we generated Jurkat clones with inducible expression of PRR7 (J-iPRR7). In these cells acute induction of PRR7 expression had a dual effect. It resulted in up-regulation of the transcription factor c-Jun and the activation marker CD69 as well as enhanced production of IL-2 after phorbol 12-myristate 13-acetate (PMA) and ionomycin treatment. On the other hand, expression of PRR7 inhibited general tyrosine phosphorylation and calcium influx after T cell receptor cross-linking by antibodies. Moreover, we found PRR7 constitutively tyrosine-phosphorylated and associated with Src. Collectively, these data indicate that PRR7 is a potential regulator of signaling and apoptosis in activated T cells.
- MeSH
- adaptorové proteiny signální transdukční biosyntéza genetika imunologie MeSH
- aminokyselinové motivy MeSH
- apoptóza účinky léků fyziologie MeSH
- Caco-2 buňky MeSH
- CD antigeny biosyntéza genetika imunologie MeSH
- diferenciační antigeny T-lymfocytů biosyntéza genetika imunologie MeSH
- fosforylace účinky léků fyziologie MeSH
- HEK293 buňky MeSH
- interleukin-2 biosyntéza genetika imunologie MeSH
- ionofory farmakologie MeSH
- ionomycin farmakologie MeSH
- Jurkat buňky MeSH
- karcinogeny farmakologie MeSH
- krysa rodu Rattus MeSH
- lektiny typu C biosyntéza genetika imunologie MeSH
- lidé MeSH
- protoonkogenní proteiny c-jun genetika imunologie metabolismus MeSH
- receptory antigenů T-buněk genetika imunologie metabolismus MeSH
- regulace genové exprese fyziologie MeSH
- T-lymfocyty imunologie metabolismus MeSH
- terciární struktura proteinů MeSH
- tetradekanoylforbolacetát farmakologie MeSH
- U937 buňky MeSH
- vápníková signalizace účinky léků fyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- adaptorové proteiny signální transdukční MeSH
- CD antigeny MeSH
- CD69 antigen MeSH Prohlížeč
- diferenciační antigeny T-lymfocytů MeSH
- IL2 protein, human MeSH Prohlížeč
- interleukin-2 MeSH
- ionofory MeSH
- ionomycin MeSH
- karcinogeny MeSH
- lektiny typu C MeSH
- protoonkogenní proteiny c-jun MeSH
- receptory antigenů T-buněk MeSH
- tetradekanoylforbolacetát MeSH