Editors' ChoiceImmunology

Rafts and Regulation

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Science's STKE  05 Apr 2005:
Vol. 2005, Issue 278, pp. tw124
DOI: 10.1126/stke.2782005tw124

Regulation of the transcription factor NF-κB is central to the activation of T cells in the immune system. Activation of the T cell receptor leads to accumulation of a group of signaling proteins within lipid rafts in the plasma membrane. Somehow this process results in activation of the IKK (IκB kinase) complex, which leads to activation of NF-κB. Lee et al. (see the Perspective by van Oers and Chen) provide a mechanism that helps link these processes. The 3-phosphoinositide-dependent kinase 1 (PDK-1) interacts with and activates another protein kinase, PKCθ, which in turn interacts with components of the IKK complex and is required for their recruitment to the lipid rafts. PDK1 also interacts with the scaffold protein CARD11, which in turn recruits the Bcl10 and MALT1 proteins. The latter proteins mediate ubiquitination of a component of the IKK complex, the signal that eventually activates NF-κB.

K.-Y. Lee, F. D'Acquisto, M. S. Hayden, J.-H. Shim, S. Ghosh, PDK1 nucleates T cell receptor-induced signaling complex for NF-κB activation. Science 308, 114-118 (2005). [Abstract] [Full Text]

N. S. C. van Oers, Z. J. Chen, Kinasing and clipping down the NF-κB trail. Science 308, 65-66 (2005). [Summary] [Full Text]