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Sci. STKE, 1 May 2007
Vol. 2007, Issue 384, p. pe19
[DOI: 10.1126/stke.3842007pe19]

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Striking Back at the Activator: How I{kappa}B Kinase Terminates Antigen Receptor Responses

Michael Hinz and Claus Scheidereit*

Max Delbrück Center for Molecular Medicine, 13092 Berlin, Germany.

Abstract: Antigen recognition by the T cell receptor (TCR) elicits several intracellular signaling cascades, one of which activates the transcription factor NF-{kappa}B through I{kappa}B kinases (IKK). NF-{kappa}B regulates lymphocyte differentiation, proliferation, and apoptosis; thus, tight temporal control of its activation is required to prevent harmful immune cell dysregulation. Although considerable insight into the IKK and NF-{kappa}B activation process has emerged, less is known about the temporal regulation and termination of immunoreceptor signaling. Two recent studies have revealed that the scaffold protein Bcl10—which, together with CARMA1 and Malt1, forms the TCR-induced IKK-activating CBM complex—is a negative feedback substrate for IKK. IKKbeta initially contributes to CBM formation—which is required for full IKK activation—and then, through carboxyl-terminal Bcl10 phosphorylation, disrupts this structure to terminate signaling. IKK triggers Bcl10 degradation by the ubiquitin-proteasome system through phosphorylation of Bcl10 at other sites. Thus, inactivation through negative feedback mechanisms is an intrinsic property of the TCR-induced NF-{kappa}B pathway.

*Corresponding author. E-mail, scheidereit{at}mdc-berlin.de

Citation: M. Hinz, C. Scheidereit, Striking Back at the Activator: How I{kappa}B Kinase Terminates Antigen Receptor Responses. Sci. STKE 2007, pe19 (2007).

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