Adenovirus Protein E4-ORF1 Activation of PI3 Kinase Reveals Differential Regulation of Downstream Effector Pathways in Adipocytes

Chaudhary, Natasha; González, Eva; Chang, Sung-Hee; Geng, Fuqiang; Rafii, Shahin; Altorki, Nasser K.; McGraw, Timothy E.

doi:10.1016/j.celrep.2016.11.082

Cited by 16 publications

(8 citation statements)

References 67 publications

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“…Nonetheless, insulin, as well as other growth factors, promote an increase of Glut1 in the plasma membrane of many cell types ( Lawrence et al, 1992 ; Egert et al, 1999 ; Rett et al, 1996 ; Clarke et al, 1994 ). To explore the behavior of Glut1 in adipocytes, we quantified plasma membrane expression using an HA-tagged Glut1 construct, a reporter used previously in studies of Glut1 trafficking ( Chaudhary et al, 2016 ; Takenouchi et al, 2007 ; Lee et al, 2015 ). In cells expressing HA-Glut1, total Glut1 was about four times that in untransfected cells, demonstrating HA-Glut1 was expressed to about three times the level of native Glut1 ( Figure 7—figure supplement 1 ).…”

Section: Resultsmentioning

confidence: 99%

Distinct Akt phosphorylation states are required for insulin regulated Glut4 and Glut1-mediated glucose uptake

Beg

Abdullah

Thowfeik

et al. 2017

eLife

132

105

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Insulin, downstream of Akt activation, promotes glucose uptake into fat and muscle cells to lower postprandial blood glucose, an enforced change in cellular metabolism to maintain glucose homeostasis. This effect is mediated by the Glut4 glucose transporter. Growth factors also enhance glucose uptake to fuel an anabolic metabolism required for tissue growth and repair. This activity is predominantly mediated by the Glut1. Akt is activated by phosphorylation of its kinase and hydrophobic motif (HM) domains. We show that insulin-stimulated Glut4-mediated glucose uptake requires PDPK1 phosphorylation of the kinase domain but not mTORC2 phosphorylation of the HM domain. Nonetheless, an intact HM domain is required for Glut4-mediated glucose uptake. Whereas, Glut1-mediated glucose uptake also requires mTORC2 phosphorylation of the HM domain, demonstrating both phosphorylation-dependent and independent roles of the HM domain in regulating glucose uptake. Thus, mTORC2 links Akt to the distinct physiologic programs related to Glut4 and Glut1-mediated glucose uptake.DOI: http://dx.doi.org/10.7554/eLife.26896.001

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Section: Resultsmentioning

confidence: 99%

Distinct Akt phosphorylation states are required for insulin regulated Glut4 and Glut1-mediated glucose uptake

Beg

Abdullah

Thowfeik

et al. 2017

eLife

132

105

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“…COG0477 catalyzes the transport of various substrates, including carbohydrates, ions, and other small molecules. It was referred to as a secondary active transporter [ 36 ]. COG1472 (hydrolase family 3) was a beta-glucosidase or beta-hexosaminidase.…”

Section: Resultsmentioning

confidence: 99%

The Genome Analysis of Methylobacterium populi YC-XJ1 with Diverse Xenobiotics Biodegrading Capacity and Degradation Characteristics of Related Hydrolase

Wang

Yang

et al. 2020

IJMS

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Methylobacterium populi YC-XJ1 isolated from desert soil exhibited a diverse degrading ability towards aromatic oxyphenoxypropionic acid esters (AOPPs) herbicide, phthalate esters (PAEs), organophosphorus flame retardants (OPFRs), chlorpyrifos and phoxim. The genome of YC-XJ1 was sequenced and analyzed systematically. YC-XJ1 contained a large number of exogenous compounds degradation pathways and hydrolase resources. The quizalofop-p-ethyl (QPE) degrading gene qpeh2 and diethyl phthalate (DEP) degrading gene deph1 were cloned and expressed. The characteristics of corresponding hydrolases were investigated. The specific activity of recombinant QPEH2 was 0.1 ± 0.02 U mg−1 for QPE with kcat/Km values of 1.8 ± 0.016 (mM−1·s−1). The specific activity of recombinant DEPH1 was 0.1 ± 0.02 U mg−1 for DEP with kcat/Km values of 0.8 ± 0.02 (mM−1·s−1). This work systematically illuminated the metabolic versatility of strain YC-XJ1 via the combination of genomics analysis and laboratory experiments. These results suggested that strain YC-XJ1 with diverse xenobiotics biodegrading capacity was a promising candidate for the bioremediation of polluted sites.

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“…In glucose-deprived states, an increase in glycogenolysis was observed in RV-infected fibroblast cells to compensate for the glucose need ( 30 ). Likewise, E4ORF1 adenovirus protein enhances insulin-stimulated PI3K signaling, followed by GLUT4 translocation to the plasma membrane in adipocytes ( 31 ).…”

Section: Glucose Metabolismmentioning

confidence: 99%

Viruses and Metabolism: The Effects of Viral Infections and Viral Insulins on Host Metabolism

et al. 2021

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Over the past decades, there have been tremendous efforts to understand the cross-talk between viruses and host metabolism. Several studies have elucidated the mechanisms through which viral infections manipulate metabolic pathways including glucose, fatty acid, protein, and nucleotide metabolism. These pathways are evolutionarily conserved across the tree of life and extremely important for the host's nutrient utilization and energy production. In this review, we focus on host glucose, glutamine, and fatty acid metabolism and highlight the pathways manipulated by the different classes of viruses to increase their replication. We also explore a new system of viral hormones in which viruses mimic host hormones to manipulate the host endocrine system. We discuss viral insulin/IGF-1-like peptides and their potential effects on host metabolism. Together, these pathogenesis mechanisms targeting cellular signaling pathways create a multidimensional network of interactions between host and viral proteins. Defining and better understanding these mechanisms will help us to develop new therapeutic tools to prevent and treat viral infections.

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Adenovirus Protein E4-ORF1 Activation of PI3 Kinase Reveals Differential Regulation of Downstream Effector Pathways in Adipocytes

Cited by 16 publications

References 67 publications

Distinct Akt phosphorylation states are required for insulin regulated Glut4 and Glut1-mediated glucose uptake

Distinct Akt phosphorylation states are required for insulin regulated Glut4 and Glut1-mediated glucose uptake

The Genome Analysis of Methylobacterium populi YC-XJ1 with Diverse Xenobiotics Biodegrading Capacity and Degradation Characteristics of Related Hydrolase

Viruses and Metabolism: The Effects of Viral Infections and Viral Insulins on Host Metabolism

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