J Biol Chem. 2003 Aug 22;278(34):31941-9. Epub 2003 May 29.

CARD6 is a modulator of NF-kappa B activation by Nod1- and Cardiak-mediated pathways.External

Stehlik, C., Hayashi, H., Pio, F., Godzik, A., Reed, J. C.,
--- - Burnham Institute, La Jolla, California 92037, USA.
We cloned a novel cDNA derived from the CARD6 gene locus on chromosome 5p12 of 311 amino acids in length. By immunoprecipitation we detected specific binding of this CARD6-encoding protein to Nod1 (CARD4), Cardiak (Rip2/Rick), NAC (NALP1/DEFCAP/CARD7), and TUCAN (CARD8/Cardinal/NDPP/Dakar), caspase recruitment domain (CARD)-containing proteins implicated in NF-kappa B and caspase-1 activation but not to other CARD family proteins. Cardiak and Nod1 (but not other CARD proteins) also exhibited opposing effects on CARD6 protein phosphorylation and expression, providing further evidence of functional interactions among these proteins in cells. In transfection experiments, the CARD6 protein suppressed NF-kappa B induction by Nod1 or Cardiak but did not interfere with NF-kappa B activation by the CARD-containing adapter protein Bcl10 or the cytokine tumor necrosis factor-alpha, demonstrating specificity of CARD6 for Nod-1 and Cardiak-dependent pathways. In contrast to its effects on Nod1- and Cardiak-dependent NF-kappa B activation, CARD6 did not interfere with caspase-1-dependent interleukin-1 beta secretion induced by Cardiak or Nod1. CARD6 also did not affect caspase activation and apoptosis induced by overexpression of Fas, Bax, or other pro-apoptotic stimuli. Thus, CARD6 represents a selective modulator of NF-kappa B activation by Cardiak and Nod1, adding to the repertoire of CARD-family proteins implicated in inflammatory responses and innate immunity.
PMID: 12775719External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vivo interaction
  Endogenous
expression
Overexpression DD1 DD2 Reference
Family DD1 DD2 Method Species Region Species Region
CARD CARD6 Link CARD8 Co-immunoprecipitation HEK293 Human 1-311 Human Full length 12775719
CARD CARD6 Link NLRP1 Co-immunoprecipitation HEK293 Human 1-311 Not specified Full length 12775719
CARD CARD6 Link NOD1 Co-immunoprecipitation HEK293 Human 1-311 Not specified Not specified 12775719
CARD CARD6 Link RIPK2 Co-immunoprecipitation HEK293 Human 1-311 Not specified Not specified 12775719
(Link: click this icon to show interactions only between the two corresponding DDs)
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
Functional Role
Family DD1 DD2 Method Death-related Death-unrelated Reference
CARD CARD6 Link NOD1 Luciferase assay NF-kB activation block 12775719
CARD CARD6 Link RIPK2 Luciferase assay NF-kB activation block 12775719
(Link: click this icon to show interactions only between the two corresponding DDs)