In: Science Signaling, 2017, vol. 10, no. 488, p. eaaf2969
The phosphoinositide 3-kinase γ (PI3Kγ) plays a major role in leukocyte recruitment during acute inflammation and has been proposed to inhibit classical macrophage activation by driving immunosuppressive gene expression. PI3Kγ plays an important role in diet-induced obesity and insulin resistance. In seeking to determine the underlying molecular mechanisms, we showed that PI3Kγ action in...
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In: Angewandte Chemie International Edition, 2014, vol. 53, no. 18, p. 4717–4720
Chemical inducers of dimerization (CIDs) have been developed to orchestrate protein dimerization and translocation. Here we present a novel photocleavable HaloTag- and SNAP-tag-reactive CID (MeNV-HaXS) with excellent selectivity and intracellular reactivity. Excitation at 360 nm cleaves the methyl-6-nitroveratryl core of MeNV-HaXS. MeNV-HaXS covalently links HaloTag- and SNAP-tag fusion...
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In: Annals of the New York Academy of Sciences, 2013, vol. 1280, p. 44-47
Phosphoinositide 3-kinase γ (PI3Kγ) plays a central role in inflammation, allergy, cardiovascular, and metabolic disease. Obesity is accompanied by chronic, low-grade inflammation. As PI3Kγ plays a major role in leukocyte recruitment, targeting of PI3Kγ has been considered to be a strategy for attenuating progression of obesity to insulin resistance and type 2 diabetes. Indeed, PI3Kγ null...
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In: Proceedings of the National Academy of Sciences of the United States of America, 2011, vol. 108, no. 42, p. E854-E863
Obesity is associated with a chronic low-grade inflammation, and specific antiinflammatory interventions may be beneficial for the treatment of type 2 diabetes and other obesity-related diseases. The lipid kinase PI3Kγ is a central proinflammatory signal transducer that plays a major role in leukocyte chemotaxis, mast cell degranulation, and endothelial cell activation. It was also reported that...
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In: Nature Reviews Molecular Cell Biology, 2008, vol. 9, p. 162-176
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In: Science, 2002, vol. 15, no. 5562, p. 2088 - 2091
The phosphoinositide phosphatase PTEN is mutated in many human cancers. Although the role of PTEN has been studied extensively, the relative contributions of its numerous potential downstream effectors to deregulated growth and tumorigenesis remain uncertain. We provide genetic evidence in Drosophila melanogaster for the paramount importance of the protein kinase Akt [also called protein...
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In: Nature, 2001, vol. 413, p. 796
The catalytic α-subunit of the enzyme phosphatidylinositol-3-OH kinase (PI(3)Kα) relays signals from G- protein-coupled receptors at the cell membrane and mediates leukocyte responses to chemokines and chemoattractants1, 2, ³. Sasaki et al.⁴ report that mice that cannot produce PI(3)Kα have a high incidence of colorectal carcinomas, causing weight loss and...
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In: FEBS Letters, 2004, vol. 577, no. 3, p. 539-544
We report here studies that integrate data of respiration rate from mouse skeletal muscle in response to leptin and pharmacological interference with intermediary metabolism, together with assays for phosphatidylinositol 3-kinase (PI3K) and AMP- activated protein kinase (AMPK). Our results suggest that the direct effect of leptin in stimulating thermogenesis in skeletal muscle is mediated by...
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In: Advances in Enzyme Regulation, 2004, vol. 44, no. 1, p. 299-308
Phosphoinositide 3-kinases (PI3K) are bifunctional enzymes expressing lipid- and protein-kinase activities. PI3K lipid kinase is involved in the control of cell motility, survival and other cellular reactions. Recent data point to specific signaling functions of PI3K protein-kinase activities. The PI3K species g has been shown to stimulate major signaling paths to the protein kinases Erk, JNK and...
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