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Involvement of GSK‐3β in TWEAK‐mediated NF‐κB activation
Author(s) -
De Ketelaere Adelheid,
Vermeulen Linda,
Vialard Jorge,
Van De Weyer Inez,
Van Wauwe Jean,
Haegeman Guy,
Moelans Inge
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.04.041
Subject(s) - gsk 3 , signal transduction , microbiology and biotechnology , nf κb , glycogen synthase , chemistry , iκbα , nucleus , inducer , cytoplasm , gsk3b , kinase , phosphorylation , biology , gene , biochemistry
Glycogen synthase kinase‐3β (GSK‐3β) is a key component of several signaling pathways. We found that a short variant of `TNF‐like weak inducer of apoptosis' (shortTWEAK) formed a complex with GSK‐3β in a yeast two‐hybrid system. We demonstrate that shortTWEAK and GSK‐3β colocalize in the nucleus of human neuroblastoma cells. We also show that TWEAK is internalized in different cell lines and that it translocates to the nucleus. This event causes the degradation of IκBα, the nuclear translocation of both GSK‐3β and p65, and the induction of NF‐κB‐driven gene expression. We demonstrate that the induction of IL‐8 expression by TWEAK can be counteracted by LiCl. Taken together, these data suggest that GSK‐3β plays an important role in the signal transduction pathway between TWEAK and NF‐κB.