ABSTRACT
Thirty-eight-negative kinase 1 (TNK1) is a member of the ACK-family of nonreceptor tyrosine kinases and was originally cloned from CD34+/Lin-/CD38-hematopoietic stem/progenitor cells. The signaling pathways induced by TNK1 are largely unknown. Here, we report that expression and consequent activation of TNK1 enables tumor necrosis factor alpha (TNFalpha)-induced apoptosis by selectively inhibiting TNFalpha-induced activation of nuclear factor-kappaB (NF-kappaB). TNK1 has no effect on NF-kappaB DNA binding or the composition of the NF-kappaB complex; however, the kinase markedly prevents TNFalpha-induced NF-kappaB transactivation. TNK1 therefore acts as a novel molecular switch that can determine the properties of TNFalpha signaling and therefore cell death.
Subject(s)
Fetal Proteins/physiology , NF-kappa B/metabolism , Protein-Tyrosine Kinases/physiology , Tumor Necrosis Factor-alpha/physiology , Apoptosis , Caspases/metabolism , HeLa Cells , Humans , Signal Transduction , Transcription Factor RelA/physiology , Transcriptional Activation , Transfection , Tumor Cells, CulturedABSTRACT
We analyzed the polymorphism for the presence/absence of the YAP element in two male Romanian samples. Frequencies of 3.7% and 10.5% were found for the presence of the element in Maramures (North Romania) and Vrancea (East Romania).
