PMID:15705585

Citation	Conti, BJ, Davis, BK, Zhang, J, O'connor, W Jr, Williams, KL and Ting, JP (2005) CATERPILLER 16.2 (CLR16.2), a novel NBD/LRR family member that negatively regulates T cell function. J. Biol. Chem. 280:18375-85
Abstract	The newly discovered mammalian CATERPILLER (NOD, NALP, PAN) family of proteins share similarities with the NBD-LRR superfamily of plant disease resistance (R) proteins and are predicted to mediate important immune regulatory function. This report describes the first cloning and characterization of a novel CATERPILLER gene, CLR16.2 that is located on human chromosome 16. The protein encoded by this gene has a typical NBD-LRR configuration. Analysis of CLR16.2 suggests the highest expression among T lymphocytes. Cellular localization studies of CLR16.2 revealed that it is a cytoplasmic protein. Querying microarray studies in the public data base showed that CLR16.2 was significantly (>90%) down-regulated 6 h after anti-CD3 and anti-CD28 stimulation of primary T lymphocytes. Its reduction upon T cell stimulation is consistent with a potential negative regulatory role. Indeed CLR16.2 decreased NF-kappaB, NFAT, and AP-1 induction of reporter gene constructs in response to T cell activation by anti-CD3 and anti-CD28 antibodies or PMA and ionomycin. Following T cell stimulation, the presence of CLR16.2 reduced the levels of the endogenous transcripts for the IL-2 and CD25 proteins that are central in maintaining T cell activation and preventing T cell anergy. This reduction was accompanied by a delay of IkappaBalpha degradation. We propose that CLR16.2 serves to attenuate T cell activation via TCR and co-stimulatory molecules, and its reduction during T cell stimulation allows the ensuing cellular activation.
Links	PubMed Online version:10.1074/jbc.M413169200
Keywords	Amino Acid Sequence; Carrier Proteins/genetics; Carrier Proteins/metabolism; Carrier Proteins/physiology; Cloning, Molecular; Down-Regulation/immunology; HeLa Cells; Humans; Intercellular Signaling Peptides and Proteins/genetics; Intercellular Signaling Peptides and Proteins/isolation & purification; Intercellular Signaling Peptides and Proteins/physiology; Intracellular Signaling Peptides and Proteins/genetics; Intracellular Signaling Peptides and Proteins/metabolism; Jurkat Cells; Membrane Proteins/genetics; Membrane Proteins/metabolism; Membrane Proteins/physiology; Molecular Sequence Data; Multigene Family; Nod2 Signaling Adaptor Protein; Oligonucleotide Array Sequence Analysis; Peptide Fragments/genetics; Peptide Fragments/metabolism; Receptors, Antigen, T-Cell/genetics; Receptors, Antigen, T-Cell/physiology; T-Lymphocytes/metabolism; T-Lymphocytes/physiology
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