This Article Full Text Full Text (PDF) Supplemental material Alert me when this article is cited Alert me if a correction is posted Citation Map Services E-mail this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by McCully, R. R. Articles by Pomerantz, J. L. Search for Related Content PubMed PubMed Citation Articles by McCully, R. R. Articles by Pomerantz, J. L.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, September 2008, p. 5668-5686, Vol. 28, No. 18
0270-7306/08/$08.00+0     doi:10.1128/MCB.00418-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

The Protein Kinase C-Responsive Inhibitory Domain of CARD11 Functions in NF-B Activation To Regulate the Association of Multiple Signaling Cofactors That Differentially Depend on Bcl10 and MALT1 for Association ^,

Ryan R. McCully and Joel L. Pomerantz^*

Department of Biological Chemistry and Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

Received 12 March 2008/ Returned for modification 15 April 2008/ Accepted 2 July 2008

The activation of NF-B by T-cell receptor (TCR) signaling is critical for T-cell activation during the adaptive immune response. CARD11 is a multidomain adapter that is required for TCR signaling to the IB kinase (IKK) complex. During TCR signaling, the region in CARD11 between the coiled-coil and PDZ domains is phosphorylated by protein kinase C (PKC) in a required step in NF-B activation. In this report, we demonstrate that this region functions as an inhibitory domain (ID) that controls the association of CARD11 with multiple signaling cofactors, including Bcl10, TRAF6, TAK1, IKK, and caspase-8, through an interaction that requires both the caspase recruitment domain (CARD) and the coiled-coil domain. Consistent with the ID-mediated control of their association, we demonstrate that TRAF6 and caspase-8 associate with CARD11 in T cells in a signal-inducible manner. Using an RNA interference rescue assay, we demonstrate that the CARD, linker 1, coiled-coil, linker 3, SH3, linker 4, and GUK domains are each required for TCR signaling to NF-B downstream of ID neutralization. Requirements for the CARD, linker 1, and coiled-coil domains in signaling are consistent with their roles in the association of CARD11 with Bcl10, TRAF6, TAK1, caspase-8, and IKK. Using Bcl10- and MALT1-deficient cells, we show that CARD11 can recruit signaling cofactors independently of one another in a signal-inducible manner.

---

* Corresponding author. Mailing address: Department of Biological Chemistry and Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Broadway Research Building, Room 607, Baltimore, MD 21205. Phone: (443) 287-3100. Fax: (443) 287-3109. E-mail: joel.pomerantz{at}jhmi.edu

Published ahead of print on 14 July 2008.

Supplemental material for this article may be found at http://mcb.asm.org/.

---

Molecular and Cellular Biology, September 2008, p. 5668-5686, Vol. 28, No. 18
0270-7306/08/$08.00+0     doi:10.1128/MCB.00418-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Moreno-Garcia, M. E., Sommer, K., Shinohara, H., Bandaranayake, A. D., Kurosaki, T., Rawlings, D. J. (2010). MAGUK-Controlled Ubiquitination of CARMA1 Modulates Lymphocyte NF-{kappa}B Activity. Mol. Cell. Biol. 30: 922-934 [Abstract] [Full Text]  
• Moreno-Garcia, M. E., Sommer, K., Haftmann, C., Sontheimer, C., Andrews, S. F., Rawlings, D. J. (2009). Serine 649 Phosphorylation within the Protein Kinase C-Regulated Domain Down-Regulates CARMA1 Activity in Lymphocytes. J. Immunol. 183: 7362-7370 [Abstract] [Full Text]