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  • 1
    Abstract: MALT1 channels proximal T-cell receptor (TCR) signalling to downstream signalling pathways. With MALT1A and MALT1B two conserved splice variants exist and we demonstrate here that MALT1 alternative splicing supports optimal T-cell activation. Inclusion of exon7 in MALT1A facilitates the recruitment of TRAF6, which augments MALT1 scaffolding function, but not protease activity. Naive CD4(+) T cells express almost exclusively MALT1B and MALT1A expression is induced by TCR stimulation. We identify hnRNP U as a suppressor of exon7 inclusion. Whereas selective depletion of MALT1A impairs T-cell signalling and activation, downregulation of hnRNP U enhances MALT1A expression and T-cell activation. Thus, TCR-induced alternative splicing augments MALT1 scaffolding to enhance downstream signalling and to promote optimal T-cell activation.
    Type of Publication: Journal article published
    PubMed ID: 27068814
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  • 2
    ISSN: 1432-1440
    Keywords: Lymphocyte activation ; immunodeficiency ; Uremia ; haemodialysis ; Lymphocytenstimulation ; Immunmangel ; Nieroninsuffizienz ; Haemodialyse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei 12 Patienten mit terminaler Niereninsuffizienz, die im chronischen Hämodialyseprogramm stehen, wurde die Stimulierbarkeit der Lymphocyten durch PHA unmittelbar vor und bei 11 Patienten nach Abschluß einer 12stündigen Dialyse bestimmt. 1 Vor der Dialyse wurde eine signifikante Reduktion der Lymphocytenstimulierbarkeit chronisch niereninsuffizienter Patienten (Median=12000 IpM,n=12) gegenüber Normalpersonen (Median=37000 IpM,n=24) gemessen. 2 Nach der Dialyse fand sich eine signifikante Steigerung der PHA-Stimulierbarkeit bei den Patienten-Lymphocyten (Median=25000 IpM,n=11). 3 Die Vitalitätsmessung der Lymphocyten ergab deutlich erniedrigte Überlebensraten bei 8 Patienten mit chronischer Niereninsuffizienz (t/2=4 Tage) gegenüber 9 Kontrollpersonen (t/2=9 Tage). 4 Auch bei Verlaufskontrollen und Untersuchungen der DNS-Synthesekinetik urämischer Lymphocyten vor und nach Dialyse bestätigte sich der steigernde Dialyseeffekt.
    Notes: Summary Lymphocytes separated from peripheral blood of twelve uraemic patients were compared with those of twenty five normal persons in their rates of DNA synthesis immediately before and twelve hours after the end of haemodialysis. 1) Before dialysis the PHA-induced DNA synthesis (Median=22000 CpM,n=12) was significantly reduced compared with normal controls (Median=37000 CpM,n=24). 2) After dialysis a significant increae in PHA activation (Median=15000 CpM,n=11) was determined. 3) The uraemic lymphocytes (8 patients) had shortened in vitro survival rates (t/2=4d) compared with lymphocytes from normal individuals (t/2=9d). 4) Follow up studies and kinetic studies of DNA synthesis of uraemic lymphocytes also demonstrated the effect of dialysis.
    Type of Medium: Electronic Resource
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