Role of glucosamine synthesis in the stimulation of TGF-alpha gene transcription by glucose and EGF

1996 ◽  
Vol 270 (3) ◽  
pp. C803-C811 ◽  
Author(s):  
M. D. Roos ◽  
I. O. Han ◽  
A. J. Paterson ◽  
J. E. Kudlow
Keyword(s):  
Growth Factor ◽  
Gene Transcription ◽  
Transforming Growth Factor ◽  
Critical Role ◽  
Transcriptional Response ◽  
Mrna Accumulation ◽  
Glucose Signaling ◽  
Alpha Gene ◽  
Stimulation Of

Transforming growth factor-alpha (TGF-alpha) gene transcription is regulated by both epidermal growth factor (EGF) and glucose. Previous studies have suggested that the metabolism of glucose to glucosamine through the enzyme L-glutamine: D-fructose-6-phosphate amidotransferase (GFAT) plays a critical role in the glucose signaling. In this paper, we compared the role of GFAT in the glucose and EGF signals. We found that, although EGF stimulates GFAT mRNA accumulation in MDA-MB-468 cells, this effect of EGF occurred several hours after TGF-alpha transcription increased. MDA-MB-468 cells also exhibited a TGF-alpha transcriptional response to low concentrations of glucose. The TGF-alpha response to glucose but not EGF could be inhibited by a blocker of GFAT activity. Blockade of GFAT was confirmed by using Western blotting with the RL2 antibody, which recognizes an epitope on proteins containing N-acetylglucosamine. Exposure of cells to glucose increased the RL2 signal on several polypeptides, but this change could be blocked by inhibition of GFAT. These results support the notion that glucose stimulation of TGF-alpha expression requires GFAT, but EGF stimulation does not.

scholarly journals The Docking Protein Gab1 Is an Essential Component of an Indirect Mechanism for Fibroblast Growth Factor Stimulation of the Phosphatidylinositol 3-Kinase/Akt Antiapoptotic Pathway

2004 ◽  
Vol 24 (13) ◽  
pp. 5657-5666 ◽  
Author(s):  
Betty Lamothe ◽  
Masashi Yamada ◽  
Ute Schaeper ◽  
Walter Birchmeier ◽  
Irit Lax ◽  
...  
Keyword(s):  
Growth Factor ◽  
Protein Kinase ◽  
Fibroblast Growth Factor ◽  
Critical Role ◽  
Mitogen Activated Protein Kinase ◽  
Fibroblast Growth ◽  
Indirect Mechanism ◽  
Docking Protein ◽  
Stimulation Of

ABSTRACT The docking protein Gab1 has been implicated as a mediator of multiple signaling pathways that are activated by a variety of receptor tyrosine kinases and cytokines. We have previously proposed that fibroblast growth factor 1 (FGF1) stimulation of tyrosine phosphorylation of Gab1 and recruitment of phosphatidylinositol (PI) 3-kinase are mediated by an indirect mechanism in which the docking protein fibroblast receptor substrate 2α (FRS2α) plays a critical role. In this report, we explore the role of Gab1 in FGF1 signaling by using mouse embryo fibroblasts (MEFs) derived from Gab1−/− or FRS2α−/− mice. We demonstrate that Gab1 is essential for FGF1 stimulation of both PI 3-kinase and the antiapoptotic protein kinase Akt, while FGF1-induced mitogen-activated protein kinase (MAPK) stimulation is not affected by Gab1 deficiency. To test the indirect mechanism for FGF1 stimulation of PI 3-kinase and Akt, we use a chimeric docking protein composed of the membrane targeting signal and the phosphotyrosine-binding domain of FRS2α fused to the C-terminal portion of Gab1, the region including the binding sites for the complement of signaling proteins that are recruited by Gab1. We demonstrate that expression of the chimeric docking protein in Gab1−/− MEFs rescues PI 3-kinase and the Akt responses, while expression of the chimeric docking protein in FRS2α−/− MEFs rescues stimulation of both Akt and MAPK. These experiments underscore the essential role of Gab1 in FGF1 stimulation of the PI 3-kinase/Akt signaling pathway and provide further support for the indirect mechanism for FGF1 stimulation of PI 3-kinase involving regulated assembly of a multiprotein complex.

scholarly journals Critical Role of Transforming Growth Factor Beta in Different Phases of Wound Healing

2013 ◽  
Vol 2 (5) ◽  
pp. 215-224 ◽  
Author(s):  
Mohammadreza Pakyari ◽  
Ali Farrokhi ◽  
Mohsen Khosravi Maharlooei ◽  
Aziz Ghahary
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Critical Role ◽  
Growth Factor Beta

scholarly journals Critical Role of Smads and AP-1 Complex in Transforming Growth Factor-β-dependent Apoptosis

2000 ◽  
Vol 275 (46) ◽  
pp. 36295-36302 ◽  
Author(s):  
Yasuko Yamamura ◽  
Xianxin Hua ◽  
Svetlana Bergelson ◽  
Harvey F. Lodish
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Critical Role ◽  
Transforming Growth Factor Β

scholarly journals Swift Is a Novel BRCT Domain Coactivator of Smad2 in Transforming Growth Factor β Signaling

2001 ◽  
Vol 21 (12) ◽  
pp. 3901-3912 ◽  
Author(s):  
Kazuya Shimizu ◽  
Pierre-Yves Bourillot ◽  
Søren J. Nielsen ◽  
Aaron M. Zorn ◽  
J. B. Gurdon
Keyword(s):  
Growth Factor ◽  
Gene Transcription ◽  
Target Genes ◽  
Transforming Growth Factor ◽  
Critical Role ◽  
Gene Activation ◽  
Transforming Growth Factor Β ◽  
Growth Factor Signaling ◽  
Dependent Manner ◽  
Tgfβ Signaling

ABSTRACT Transforming growth factor β (TGFβ) signaling is transduced via Smad2–Smad4–DNA-binding protein complexes which bind to responsive elements in the promoters of target genes. However, the mechanism of how the complexes activate the target genes is unclear. Here we identify Xenopus Swift, a novel nuclear BRCT (BRCA1 C-terminal) domain protein that physically interacts with Smad2 via its BRCT domains. We examine the activity of Swift in relation to gene activation in Xenopus embryos. Swift mRNA has an expression pattern similar to that of Smad2. Swift has intrinsic transactivation activity and activates target gene transcription in a TGFβ-Smad2-dependent manner. Inhibition of Swift activity results in the suppression of TGFβ-induced gene transcription and defective mesendoderm development. Blocking Swift function affects neither bone morphogenic protein nor fibroblast growth factor signaling during early development. We conclude that Swift is a novel coactivator of Smad2 and that Swift has a critical role in embryonic TGFβ-induced gene transcription. Our results suggest that Swift may be a general component of TGFβ signaling.

scholarly journals Critical role of C/EBPδ and C/EBPβ factors in the stimulation of the cyclooxygenase-2 gene transcription by interleukin-1β in articular chondrocytes

2000 ◽  
Vol 267 (23) ◽  
pp. 6798-6809 ◽  
Author(s):  
Béatrice Thomas ◽  
Francis Berenbaum ◽  
Lydie Humbert ◽  
Huimin Bian ◽  
Gilbert Béréziat ◽  
...  
Keyword(s):  
Gene Transcription ◽  
Articular Chondrocytes ◽  
Critical Role ◽  
Cyclooxygenase 2 ◽  
Interleukin 1Β ◽  
Stimulation Of
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