Immunology Innate and Adaptive Immunity

Analysis of a specific signaling molecule in the immune system has shed new light on the evolution of the immune system. The IB kinase (IKK) complex plays a critical role in inflammation. One of its catalytic subunits, IKKβ, is essential for phosphorylation of the inhibitory IB protein and consequent activation of the nuclear factor B (NF-B) transcription factor. The physiological role of the other subunit, IKKα, has been less clear (see Perspective by DiDonato ). Senftleben et al. studied irradiated mice in which the bone marrow was reconstituted from stem cells lacking IKKα or with mutations in that protein. They show that IKKα is required for maturation of B cells, the formation of secondary lymphoid organs, and the normal processing of NF-B2 (also called p100) into its mature form, p52. IKKα appears to phosphorylate NF-B2 directly and thus stimulate its processing. This role for IKKα is similar to that of the single IKK expressed in Drosophila; however, the Drosophila protein functions in innate immune responses to bacterial infection, whereas in mammals, the duplicated forms of IKK mediate distinct processes in adaptive immunity.

U. Senftleben, Y. Cao, G. Xiao, F. R. Greten, G. Krähn, G. Bonizzi, Y. Chen, Y. Hu, A. Fong, S.-C. Sun, M. Karin. Activation by IKKα of a second, evolutionary conserved, NF-B signaling pathway. Science 293, 1495-1499 (2001). [Abstract] [Full Text]

J. A. DiDonato, IKKα on center stage. Science's STKE (2001), http://stke.sciencemag.org/cgi/content/full/OC_sigtrans;2001/97/pe1 [Abstract] [Full Text]