• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

NF-kappaB activation in T cells requires discrete control of IkappaB kinase alpha/beta (IKKalpha/beta) phosphorylation and IKKgamma ubiquitination by the ADAP adapter protein.

NF-kappaB activation following engagement of the antigen-specific T cell receptor involves protein kinase C-theta-dependent assembly of the CARMA1-BCL10-MALT1 (CBM) signalosome, which coordinates downstream activation of IkappaB kinase (IKK). We previously identified a novel role for the adhesion- and degranulation-promoting adapter protein (ADAP) in regulating the assembly of the CBM complex via an interaction of ADAP with CARMA1. In this study, we identify a novel site in ADAP that is critical for association with the TAK1 kinase. ADAP is critical for recruitment of TAK1 and the CBM complex, but not IKK, to protein kinase C-theta. ADAP is not required for TAK1 activation. Although both the TAK1 and the CARMA1 binding sites in ADAP are essential for IkappaB alpha phosphorylation and degradation and NF-kappaB nuclear translocation, only the TAK1 binding site in ADAP is necessary for IKK phosphorylation. In contrast, only the CARMA1 binding site in ADAP is required for ubiquitination of IKKgamma. Thus, distinct sites within ADAP control two key activation responses that are required for NF-kappaB activation in T cells.

Pubmed ID: 20164171

Authors

  • Srivastava R
  • Burbach BJ
  • Shimizu Y

Journal

The Journal of biological chemistry

Publication Data

April 9, 2010

Associated Grants

  • Agency: NIAID NIH HHS, Id: R01 AI031126
  • Agency: NIAID NIH HHS, Id: R01 AI038474
  • Agency: NIAID NIH HHS, Id: R01 AI038474

Mesh Terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Binding Sites
  • CARD Signaling Adaptor Proteins
  • Gene Expression Regulation, Enzymologic
  • Guanylate Cyclase
  • Humans
  • I-kappa B Kinase
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • NF-kappa B
  • Phosphorylation
  • Receptors, Antigen, T-Cell
  • Signal Transduction
  • T-Lymphocytes
  • Transcription Factors