Disease relevance of Gpr65

• Using gene expression profiles of lymphoma cell lines and primary thymocytes treated with the synthetic glucocorticoid dexamethasone, we discovered that induction of tdag8 (T-cell death-associated gene 8) was a common event in each model system investigated [1].

High impact information on Gpr65

• Furthermore, TDAG8 KO thymocytes showed normal apoptosis following in vivo and in vitro GC treatment [2].
• T-cell death-associated gene 8 (TDAG8) is a G-protein-coupled receptor transcriptionally upregulated by glucocorticoids (GCs) and implicated by overexpression studies in psychosine-mediated inhibition of cytokinesis and in GC-induced apoptosis [2].
• In contrast to previous overexpression results, TDAG8 was dispensable for psychosine-induced formation of multinucleated cells [2].
• Together, these data suggest that TDAG8 is a regulator of glucocorticoid-induced apoptosis and that agonists of TDAG8 may be promising agents to improve the efficacy of glucocorticoids for the treatment of leukemia and lymphoma [1].
• Expression of a TDAG8-GFP fusion protein was sufficient to induce apoptosis, and repression of endogenous TDAG8 using RNA interference partially inhibited dexamethasone-induced apoptosis [1].

Biological context of Gpr65

• These results, while establishing a useful reporter strain to study T-lymphocyte maturation, argue against a critical role for TDAG8 in immune development, psychosine-mediated inhibition of cytokinesis, and GC-induced cell death [2].
• The tissue-specific expression of TDAG8 and the induction of its expression during cell death of T cells mediated by the TCR or glucocorticoids suggest that it may have a role in activation-induced cell death or differentiation of T cells [3].

Anatomical context of Gpr65

• In mice, TDAG8 is predominantly expressed in thymus and spleen [3].

Associations of Gpr65 with chemical compounds

• The expression of TDAG8 is greatly induced upon activation of T cells by anti-TCR antibody or by phorbol 12-myristate 13-acetate plus ionomycin [3].
• Here, we present data that TDAG8 expression is induced prior to induction of DEX-mediated apoptosis [4].

Other interactions of Gpr65

• Using the technique of differential mRNA display, we have identified a novel gene, TDAG8, which encodes a putative G protein-coupled receptor [3].
• Moreover, activation of caspase-3, -8 and -9 was enhanced in thymocytes of TDAG8 transgenic mice after DEX stimulation [4].
• In conclusion, TDAG8 expression is involved in glucocorticoid-induced signals to activate caspase-9, -8 and -3 for subsequent apoptosis induction in CD4(+)CD8(+) double-positive thymocytes [4].

References