CARMA1 coiled-coil domain is involved in the oligomerization and subcellular localization of CARMA1 and is required for T cell receptor-induced NF-kappaB activation

J Biol Chem. 2007 Jun 8;282(23):17141-7. doi: 10.1074/jbc.M700169200. Epub 2007 Apr 11.

Abstract

T lymphocyte (T cell) activation and proliferation is induced by the activation of multiple signal transduction pathways. Earlier studies indicate that CARMA1, a Caspase Recruitment Domain (CARD) and Membrane-associated GUanylate Kinase domain (MAGUK)-containing scaffold protein, plays an essential role in NF-kappaB activation induced by the costimulation of T cell receptor (TCR) and CD28 molecules. However, the molecular mechanism by which CARMA1 mediates TCR-CD28 costimulation-induced NF-kappaB activation is not fully understood. Here we show that CARMA1 is constitutively oligomerized. This oligomerization of CARMA1 is through its Coiled-coil domain. Disruption of the predicted structure of the Coiled-coil domain of CARMA1 impaired its oligomerization and, importantly, abrogated CARMA1-mediated NF-kappaB activation. Interestingly, disruption of the CC1 domain abrogates CARMA1 localization, whereas disruption of the CC2 domain seems to inhibit CARMA1 self-association. Together, our results demonstrate that the oligomerization of CARMA1 is required for TCR-induced NF-kappaB activation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / chemistry
  • Apoptosis Regulatory Proteins / metabolism
  • Apoptosis Regulatory Proteins / physiology*
  • Biopolymers / chemistry
  • Biopolymers / metabolism
  • Biopolymers / physiology*
  • CARD Signaling Adaptor Proteins / chemistry
  • CARD Signaling Adaptor Proteins / metabolism
  • CARD Signaling Adaptor Proteins / physiology*
  • Cell Line
  • Humans
  • Mice
  • NF-kappa B / metabolism*
  • Receptors, Antigen, T-Cell / physiology*
  • Subcellular Fractions / metabolism*
  • Two-Hybrid System Techniques

Substances

  • Apoptosis Regulatory Proteins
  • Biopolymers
  • CARD Signaling Adaptor Proteins
  • Card11 protein, mouse
  • NF-kappa B
  • Receptors, Antigen, T-Cell