A novel pleckstrin homology-related gene family defined by Ipl/Tssc3, TDAG51, and Tih1: tissue-specific expression, chromosomal location, and parental imprinting

Frank, Dale; Mendelsohn, Cathy; Ciccone, Emilio; Svensson, Kristian; Ohlsson, Rolf; Tycko, Benjamin

doi:10.1007/s003359901182

Cited by 99 publications

(98 citation statements)

References 27 publications

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“…However, although considered proapoptotic, TDAG51 is also up-regulated by IGF-I (48) and platelet-derived growth factor (51) through the activation of the Akt pathway (51), which is strongly involved in survival. TDAG51 regulation by IR-A may reflect a mechanism common to different growth factors and may underscore the fact that apoptosis is also regulated by the IR-A isoform, by both proapoptotic and antiapoptotic factors, as shown previously for IGF-IR (44,52,53).…”

Section: Differential Transcriptional Effects Of Insulin and Igf-ii 4supporting

confidence: 54%

Differential Gene Expression Induced by Insulin and Insulin-like Growth Factor-II through the Insulin Receptor Isoform A

Pandini

Medico

Conte

et al. 2003

Journal of Biological Chemistry

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The human insulin receptor (IR) exists in two isoforms (IR-A and IR-B). IR-A is a short isoform, generated by the skipping of exon 11, a small exon encoding for 12 amino acid residues at the carboxyl terminus of the IR ␣-subunit. Recently, we found that IR-A is the predominant isoform in fetal tissues and malignant cells and binds with a high affinity not only insulin but also insulin-like growth factor-II (IGF-II). To investigate whether the activation of IR-A by the two ligands differentially activate post-receptor molecular mechanisms, we studied gene expression in response to IR-A activation by either insulin or IGF-II, using microarray technology. To avoid the interfering effect of the IGF-IR, IGF-II binding to the IR-A was studied in IGF-IR-deficient murine fibroblasts (R ؊ cells) transfected with the human IR-A cDNA (R؊ /IR-A cells). Gene expression was studied at 0.5, 3, and 8 h. We found that 214 transcripts were similarly regulated by insulin and IGF-II, whereas 45 genes were differentially transcribed. Eighteen of these differentially regulated genes were responsive to only one of the two ligands (12 to insulin and 6 to IGF-II). Twenty-seven transcripts were regulated by both insulin and IGF-II, but a significant difference between the two ligands was present at least in one time point. Interestingly, IGF-II was a more potent and/or persistent regulator than insulin for these genes. Results were validated by measuring the expression of 12 genes by quantitative real-time reverse transcriptase-PCR. In conclusion, we show that insulin and IGF-II, acting via the same receptor, may differentially affect gene expression in cells. These studies provide a molecular basis for understanding some of the biological differences between the two ligands and may help to clarify the biological role of IR-A in embryonic/fetal growth and the selective biological advantage that malignant cells producing IGF-II may acquire via IR-A overexpression.

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Section: Differential Transcriptional Effects Of Insulin and Igf-ii 4supporting

confidence: 54%

Differential Gene Expression Induced by Insulin and Insulin-like Growth Factor-II through the Insulin Receptor Isoform A

Pandini

Medico

Conte

et al. 2003

Journal of Biological Chemistry

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“…TDAG51 is a member of a novel pleckstrin homology-related 2 J. Zhou and R. C. Austin, manuscript in preparation gene family that consists of Ipl/Tssc and Tih (20). Sequence analysis has revealed that TDAG51 contains a central motif resembling a pleckstrin homology domain and several distinctive C-terminal proline-glutamine and proline-histidine repeats, suggesting a role in transcriptional regulation and/or PCD (21,22).…”

Section: Discussionmentioning

confidence: 99%

TDAG51 Is Induced by Homocysteine, Promotes Detachment-mediated Programmed Cell Death, and Contributes to the Development of Atherosclerosis in Hyperhomocysteinemia

Hossain

Thienen

Werstuck

et al. 2003

Journal of Biological Chemistry

207

194

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Hyperhomocysteinemia is an independent risk factor for cardiovascular disease and accelerates atherosclerosis in apoE ؊/؊ mice. Despite the observations that homocysteine causes endoplasmic reticulum (ER) stress and programmed cell death (PCD) in cultured human vascular endothelial cells, the cellular factors responsible for this effect and their relevance to atherogenesis have not been completely elucidated. We report here that homocysteine induces the expression of T-cell death-associated gene 51 (TDAG51), a member of the pleckstrin homology-related domain family, in cultured human vascular endothelial cells. This effect was observed for other ER stress-inducing agents, including dithiothreitol and tunicamycin. TDAG51 expression was attenuated in homozygous A/A mutant eukaryotic translation initiation factor 2␣ mouse embryonic fibroblasts treated with homocysteine or tunicamycin, suggesting that ER stress-induced phosphorylation of eukaryotic translation initiation factor 2␣ is required for TDAG51 transcriptional activation. Transient overexpression of TDAG51 elicited significant changes in cell morphology, decreased cell adhesion, and promoted detachmentmediated PCD. In support of these in vitro findings, TDAG51 expression was increased and correlated with PCD in the atherosclerotic lesions from apoE ؊/؊ mice fed hyperhomocysteinemic diets, compared with mice fed a control diet. Collectively, these findings provide evidence that TDAG51 is induced by homocysteine, promotes detachment-mediated PCD, and contributes to the development of atherosclerosis observed in hyperhomocysteinemia.

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“…This view, however, has been challenged by the observation that T-cells from TDAG51 À/À mice do not display discernible defects in CD3/ TCR-dependent upregulation of CD95 expression or AICD. 13 Since there are several pleckstrin-homology domain-containing proteins with significant homology to TDAG51, [18][19][20][21] it might be possible that one of these homologues fulfills the role ascribed to TDAG51 in normal murine and human T-cells. In line with a dispensable role of TDAG51 in the regulation of AICD, we did not observe a correlation between TDAG51 expression and the induction of AICD in a set of AICDsusceptible and AICD-resistant human T-cell clones.…”

Section: Discussionmentioning

confidence: 99%

Regulation of T-cell death-associated gene 51 (TDAG51) expression in human T-cells

et al. 2004

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T-cell death-associated gene 51 (TDAG51) has been described to regulate T-cell receptor/CD3-dependent induction of CD95/ Fas and subsequent activation-induced cell death (AICD) in a murine T-cell hybridoma. Using well-defined pharmacological inhibitors, we investigated the regulation of TDAG51 expression in human T-cells and the correlation with cell death. TDAG51 was induced in resting T-cells, lymphoid cell lines and AICD-susceptible as well as AICD-resistant T-cell clones, and induction was inhibited by MAP-kinase inhibitors and PKC inhibitor Gö 6983. No correlation between the effects of inhibitors on TDAG51 expression and cell death was observed. The constitutive TDAG51 expression in five pancreatic carcinoma cell lines was reduced by MAP-kinase inhibitors but not by Gö 6983. Furthermore, the inducible overexpression of TDAG51 in TetOn Jurkat cells did not modulate cellular proliferation, phorbolester/ionomycin-induced growth arrest, or the expression of various cell surface molecules. Our results indicate that the expression of TDAG51 in human T-cells does not correlate with AICD.

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A novel pleckstrin homology-related gene family defined by Ipl/Tssc3, TDAG51, and Tih1: tissue-specific expression, chromosomal location, and parental imprinting

Cited by 99 publications

References 27 publications

Differential Gene Expression Induced by Insulin and Insulin-like Growth Factor-II through the Insulin Receptor Isoform A

Differential Gene Expression Induced by Insulin and Insulin-like Growth Factor-II through the Insulin Receptor Isoform A

TDAG51 Is Induced by Homocysteine, Promotes Detachment-mediated Programmed Cell Death, and Contributes to the Development of Atherosclerosis in Hyperhomocysteinemia

Regulation of T-cell death-associated gene 51 (TDAG51) expression in human T-cells

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