Detection of IKKbeta-IKKgamma subcomplexes in monocytic cells and characterization of associated signaling

The Journal of Biological Chemistry
Martina QuirlingK Brand

Abstract

The IkappaB kinase (IKK) complex is one major step in the regulation of the NF-kappaB/Rel system that is involved in inflammatory and immune responses as well as in proliferation and apoptosis. At present it is not clear whether besides the "classical" IKKalpha-IKKbeta-IKKgamma configuration additional complexes exist in vivo that solely contain IKKbeta and IKKgamma (without IKKalpha). In the current study we were able to demonstrate in monocytic cells that endogenous complexes, which only include IKKbeta as the kinase-active molecule do indeed exist in vivo and that these complexes contain IKKgamma as an additional component. Furthermore, we showed that these IKKbeta-IKKgamma complexes are involved in mainstream NF-kappaB activation cascades because they can be activated by tumor necrosis factor. In contrast, these subcomplexes appear not to participate in NIK-dependent pathways. As a next step we showed that exogenous IKKbeta-IKKgamma complexes can be formed in an intact cell by overexpression and that these artificial complexes fulfill the requirement for participation in regular signaling. Finally, in the absence of IKKalpha we found a retarded proteolysis of IkappaBalpha, but not of IkappaB in, which is associated with a r...Continue Reading

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Citations

Aug 1, 2012·Frontiers in Biology·Yonggang Zhang, Wenhui Hu
Oct 21, 2006·Arteriosclerosis, Thrombosis, and Vascular Biology·Christian CappelloKorbinian Brand
Feb 2, 2006·International Journal of Cancer. Journal International Du Cancer·Vijayabaskar LakshmikanthanM Vijay Kumar
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Dec 16, 2005·Neoplasia : an International Journal for Oncology Research·Robert B ShirleyM Vijay Kumar

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