Expression of serum- and glucocorticoid-regulated kinase (<i>sgk</i>) mRNA is up-regulated by GM-CSF and other proinflammatory mediators in human granulocytes

Cowling, Randy T.; Birnboim, H.C.

doi:10.1002/jlb.67.2.240

Cited by 41 publications

(31 citation statements)

References 79 publications

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“…It is overexpressed in hepatocellular carcinoma and tumorigenic cell lines (83,84) and is induced by granulocyte-macrophage colonystimulating factor in human granulocytes (85).…”

Section: Nup98-hoxa9 and Malignant Transformationmentioning

confidence: 99%

The Oncogene Nup98-HOXA9 Induces Gene Transcription in Myeloid Cells

Ghannam

Takeda

Camarata

et al. 2004

Journal of Biological Chemistry

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The nucleoporin Nup98 gene is frequently rearranged in acute myelogenous leukemia (AML). In most cases this results in fusion of the N terminus of Nup98 to the DNA binding domain of a homeodomain transcription factor. The prototype of these fusions, Nup98-HOXA9, is associated with human AML and induces AML in mouse models. To understand the mechanisms by which Nup98-HOXA9 causes AML, we expressed it in myeloid cells and identified its target genes using high density oligonucleotide microarrays. The analysis was performed in triplicate and was confirmed by quantitative real time PCR. Of the 102 Nup98-HOXA9 target genes identified, 92 were up-regulated, and only 10 were downregulated, suggesting a transcriptional activation function. A similar analysis of wild-type HOXA9 revealed 13 target genes, 12 of which were up-regulated, and 1 was down-regulated. In contrast, wild-type Nup98 had no effect on gene expression, demonstrating that the HOXA9 DNA binding domain is required for gene regulation. Co-transfection experiments using a luciferase reporter linked to the promoter of one of the Nup98-HOXA9 target genes confirmed up-regulation at the transcriptional level by Nup98-HOXA9 but not by either HOXA9 or Nup98. These data indicate that Nup98-HOXA9 is an aberrant transcription factor whose activity depends on the HOXA9 DNA binding domain but has a stronger and wider transcriptional effect than HOXA9. Several of the genes regulated by Nup98-HOXA9 are associated with increased cell proliferation and survival as well as drug metabolism, providing insights into the pathogenesis and epidemiology of Nup98-HOXA9-induced AML.

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“…It is overexpressed in hepatocellular carcinoma and tumorigenic cell lines (83,84) and is induced by granulocyte-macrophage colonystimulating factor in human granulocytes (85).…”

Section: Nup98-hoxa9 and Malignant Transformationmentioning

confidence: 99%

The Oncogene Nup98-HOXA9 Induces Gene Transcription in Myeloid Cells

Ghannam

Takeda

Camarata

et al. 2004

Journal of Biological Chemistry

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“…The mRNA encoding SGK1, the best-studied member of the SGK family, is rapidly induced in response to a variety of stimuli, including growth factors (51,52), steroid and peptide hormones (3,51,52), cytokines (15,50), changes in cell volume (49), and brain injury (24).…”

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confidence: 99%

Protein Kinase SGK Mediates Survival Signals by Phosphorylating the Forkhead Transcription Factor FKHRL1 (FOXO3a)

et al. 2001

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Serum-and glucocorticoid-inducible kinases (SGKs) form a novel family of serine/threonine kinases that are activated in response to a variety of extracellular stimuli. SGKs are related to Akt (also called PKB), a serine/threonine kinase that plays a crucial role in promoting cell survival. Like Akt, SGKs are activated by the phosphoinositide-3 kinase (PI3K) and translocate to the nucleus upon growth factor stimulation. However the physiological substrates and cellular functions of SGKs remained to be identified. We hypothesized that SGKs regulate cellular functions in concert with Akt by phosphorylating common targets within the nucleus. The best-characterized nuclear substrates of Akt are transcription factors of the Forkhead family. Akt phosphorylates Forkhead transcription factors such as FKHRL1, leading to FKHRL1's exit from the nucleus and the consequent shutoff of FKHRL1 target genes. We show here that SGK1, like Akt, promotes cell survival and that it does so in part by phosphorylating and inactivating FKHRL1. However, SGK and Akt display differences with respect to the efficacy with which they phosphorylate the three regulatory sites on FKHRL1. While both kinases can phosphorylate Thr-32, SGK displays a marked preference for Ser-315 whereas Akt favors Ser-253. These findings suggest that SGK and Akt may coordinately regulate the function of FKHRL1 by phosphorylating this transcription factor at distinct sites. The efficient phosphorylation of these three sites on FKHRL1 by SGK and Akt appears to be critical to the ability of growth factors to suppress FKHRL1-dependent transcription, thereby preventing FKHRL1 from inducing cell cycle arrest and apoptosis. These findings indicate that SGK acts in concert with Akt to propagate the effects of PI3K activation within the nucleus and to mediate the biological outputs of PI3K signaling, including cell survival and cell cycle progression.Serum-and glucocorticoid-induced kinases (SGKs) belong to a new family of serine/threonine kinases that are regulated at both the transcriptional and posttranslational levels by external stimuli. The mRNA encoding SGK1, the best-studied member of the SGK family, is rapidly induced in response to a variety of stimuli, including growth factors (51, 52), steroid and peptide hormones (3, 51, 52), cytokines (15, 50), changes in cell volume (49), and brain injury (24).The SGK gene is conserved from yeast to human, and the SGK protein is expressed in a variety of tissues and cell lines in mammals (10, 51, 52). Although it has been proposed that SGK may play a role in cell cycle progression (8) or sodium homeostasis control (4, 12), the cellular functions of SGK are largely uncharacterized, and to date no in vivo SGK substrates have been identified.Within the protein kinase superfamily, SGK is closely related to Akt (also called PKB), another serine/threonine kinase that is activated in response to growth and survival factors and plays a critical role in promoting cell survival (16,20). Several recent reports have shown that growth and s...

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“…The kinase was originally cloned as a glucocorticoid-sensitive gene (34) but later shown to be similarly regulated by mineralocorticoids (5,19,23,29,38,42,50,53,57,70), gonadotropins (24,36,63,64,67), 1,25-dihydroxyvitamin D 3 (1), transforming growth factor-␤ (44, 83), interleukin-6 (54), fibroblast and platelet-derived growth factor (56), thrombin (4), and endothelin (85), as well as other cytokines (25,47,79). SGK1 transcription has further been shown to be stimulated by cell shrinkage (82), cell swelling (65), heat shock, UV radiation, and oxidative stress (51).…”

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confidence: 99%