Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

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

PERSPECTIVES

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).

Read the Full Text



To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882