Disease relevance of Art2b

• Using lymphoma transfectants expressing either ART2.2 with its native GPI anchor (ART2.2-GPI) or ART2.2 with a grafted transmembrane anchor (ART2.2-Tm), we demonstrated that ART2.2-GPI but not ART2.2-Tm associated with glycosphingolipid-enriched microdomains (lipid rafts) [1].

High impact information on Art2b

• T cells express ART2.2, a toxin-related, glycosylphosphatidylinositol (GPI)-anchored ecto-enzyme [1].
• RT-PCR analyses revealed that resting BALB/c T cells expressed the genes for GPI-anchored ART2.1 and ART2.2 but not ART1 [2].
• In the thymus, ART2.2 expression is restricted to subpopulations of mature cells [3].
• Recombinant C57BL/6 Rt6-2 and BALB/c Rt6-1 proteins expressed in COS1 cells exhibited ART activity and were documented to be glycosylphosphatidylinositol-linked membrane proteins [4].
• Predicted amino acid sequences of Rt6-2 were identical in both strains, but there was an in-frame stop codon in the sequence of Rt6-1 in C57BL/6 mice not present in BALB/c mice [4].

Biological context of Art2b

• The nucleotide sequences of the Rt6-1 and Rt6-2 coding regions show 87% sequence identity, the deduced amino acid sequences 79% identity [5].
• The two mouse Rt6 genes (designated Rt6-1 and Rt6-2) encode similar open reading frames that are disrupted by conserved introns [5].
• Since the NZW mouse does not show any gross immunological abnormalities, loss of the Rt6-2 gene by itself is not associated with any obvious immunological phenotype [6].
• Molecular polymorphism in the Rt6 genes of laboratory mice correlates with the allotypes of the H1 minor histocompatibility system [7].

Anatomical context of Art2b

• Mouse T-cell antigens Rt6.1 and Rt6.2 are glycosylphosphatidylinositol-anchored arginine-specific adenosine diphosphate (ADP)-ribosyltransferases [8].
• The expression of Rt6-1 and Rt6-2 mRNAs in lymphoid tissues suggests that these ARTs may regulate immune system functions [4].

Associations of Art2b with chemical compounds

• Purified recombinant Rt6-2, but not Rt6-1, shows NAD+ glycohydrolase activity, which is inhibited by the arginine analogue agmatine [9].
• Without an added ADP-ribose acceptor, Rt6.2 shows NAD glycohydrolase (NADase) activity [10].
• Compared with Rt6.2, Rt6.1 has two extra cysteine residues at positions 80 and 201 [10].
• When Cys-80 and Cys-201 in Rt6.1 were replaced with the corresponding residues of Rt6.2, serine and phenylalanine, respectively, Rt6.1 catalyzed the NADase reaction even in the absence of DTT [10].
• We analysed temporal changes in ART2.2 expression in unmanipulated and cyclophosphamide-treated NOD/Lt mice compared with diabetes-resistant control strains [11].

Regulatory relationships of Art2b

• We show that ART2.2 is expressed as a GPI-anchored protein on the surface of mature T cells [3].

Other interactions of Art2b

• Mouse T cell membrane proteins Rt6-1 and Rt6-2 are arginine/protein mono(ADPribosyl)transferases and share secondary structure motifs with ADP-ribosylating bacterial toxins [9].

Analytical, diagnostic and therapeutic context of Art2b

• Immunoprecipitation of recombinant Rt6-1 and Rt6-2 with anti-FLAG M2 antibody followed by incubation with [32P]NAD+ leads to rapid and covalent incorporation of radioactivity into the light chain of the M2 antibody [9].
• Southern blot and sequence analyses revealed that NZW mice have suffered a deletion of the Rt6.2 gene while the Rt6-1 gene of BxSB mice has been inactivated by a premature stop codon [6].
• ART2.2 shed from activated T cells migrates slightly faster in SDS-PAGE analyses than does ART2.2 released upon cleavage of the GPI anchor [12].
• METHODS: ART2.2 and CD38, another NAD-utilizing enzyme, were measured by flow cytometry [11].

References