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10 results on '"Low, Pei Ching"'

2. Phosphoinositide 3-kinase [delta] regulates membrane fission of Golgi carriers for selective cytokine secretion

Author

Low, Pei Ching, Misaki, Ryo, Schroder, Kate, Stanley, Amanda C., Sweet, Matthew J., Teasdale, Rohan D., Vanhaesebroeck, Bart, Meunier, Frederic A., Taguchi, Tomohiko, and Stow, Jennifer L.

Subjects
Cytokines -- Research, Phosphotransferases -- Research, Cell membranes -- Research, Golgi apparatus -- Research, Biological sciences
Abstract

Phosphoinositide 3-kinase (PI3K) p110 isoforms are membrane lipid kinases classically involved in signal transduction. Lipopolysaccharide (LPS)-activated macrophages constitutively and abundantly secrete proinflammatory cytokines including tumor necrosis factor-[alpha] (TNF). Loss of function of the p110[delta] isoform of PI3K using inhibitors, RNA-mediated knockdown, or genetic inactivation in mice abolishes TNF trafficking and secretion, trapping TNF in tubular carriers at the trans-Golgi network (TGN). Kinase-active p110[delta] localizes to the Golgi complex in LPS-activated macrophages, and TNF is loaded into p230-labeled tubules, which cannot undergo fission when p110[delta] is inactivated. Similar blocks in fission of these tubules and in TNF secretion result from inhibition of the guanosine triphosphatase dynamin 2. These findings demonstrate a new function for p110[delta] as part of the membrane fission machinery required at the TGN for the selective trafficking and secretion of cytokines in macrophages. doi/ 10.1083/jcb.201001028

Published
2010

3. Inactivation of the Class II PI3K-C2β Potentiates Insulin Signaling and Sensitivity

Author

Alliouachene, Samira, Bilanges, Benoit, Chicanne, Gaëtan, Anderson, Karen E., Pearce, Wayne, Ali, Khaled, Valet, Colin, Posor, York, Low, Pei Ching, Chaussade, Claire, Scudamore, Cheryl L., Salamon, Rachel S., Backer, Jonathan M., Stephens, Len, Hawkins, Phill T., Payrastre, Bernard, and Vanhaesebroeck, Bart

Subjects
Blood Glucose, Endosomes, Diet, High-Fat, Article, Fatty Liver, Mice, Inbred C57BL, Mice, lcsh:Biology (General), Liver, Autophagy, Hepatocytes, Animals, Insulin, Gene Knock-In Techniques, Mitogen-Activated Protein Kinases, Phosphorylation, lcsh:QH301-705.5, Proto-Oncogene Proteins c-akt, Cells, Cultured, Adaptor Proteins, Signal Transducing, Class II Phosphatidylinositol 3-Kinases, Signal Transduction
Abstract

Summary In contrast to the class I phosphoinositide 3-kinases (PI3Ks), the organismal roles of the kinase activity of the class II PI3Ks are less clear. Here, we report that class II PI3K-C2β kinase-dead mice are viable and healthy but display an unanticipated enhanced insulin sensitivity and glucose tolerance, as well as protection against high-fat-diet-induced liver steatosis. Despite having a broad tissue distribution, systemic PI3K-C2β inhibition selectively enhances insulin signaling only in metabolic tissues. In a primary hepatocyte model, basal PI3P lipid levels are reduced by 60% upon PI3K-C2β inhibition. This results in an expansion of the very early APPL1-positive endosomal compartment and altered insulin receptor trafficking, correlating with an amplification of insulin-induced, class I PI3K-dependent Akt signaling, without impacting MAPK activity. These data reveal PI3K-C2β as a critical regulator of endosomal trafficking, specifically in insulin signaling, and identify PI3K-C2β as a potential drug target for insulin sensitization., Graphical Abstract, Highlights • PI3K-C2β kinase-dead mice are viable with enhanced glucose tolerance • PI3K-C2β inactivation sensitizes to insulin and protects from liver steatosis • PI3K-C2β inactivation selectively enhances insulin/Akt signaling in metabolic tissues • PI3K-C2β activity regulates very early endosomal compartments in hepatocytes, Organismal roles of class II PI3Ks are unclear. Alliouachene et al. show that inactivation of the class II PI3K-C2β in mice, by regulating insulin receptor trafficking, enhances insulin sensitivity and protects against high-fat-diet-induced liver steatosis. The results suggest that PI3K-C2β is a potential drug target for insulin sensitization.

Published
2014

4. Inactivation of the Class II PI3K-C2β Potentiates Insulin Signaling and Sensitivity

Author

Alliouachene, Samira, primary, Bilanges, Benoit, additional, Chicanne, Gaëtan, additional, Anderson, Karen E., additional, Pearce, Wayne, additional, Ali, Khaled, additional, Valet, Colin, additional, Posor, York, additional, Low, Pei Ching, additional, Chaussade, Claire, additional, Scudamore, Cheryl L., additional, Salamon, Rachel S., additional, Backer, Jonathan M., additional, Stephens, Len, additional, Hawkins, Phill T., additional, Payrastre, Bernard, additional, and Vanhaesebroeck, Bart, additional

Published
2015
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5. 119

Author

Low, Pei Ching (Regine), primary, Manzanero, Silvia, additional, Narayana, Vinod K., additional, Nguyen, Tam H., additional, Kvaskoff, David, additional, Brennan, Faith H., additional, Ruitenberg, Marc J., additional, Gelderblom, Mathias, additional, Magnus, Tim, additional, Kim, Hyun Ah, additional, Broughton, Brad R.S., additional, Sobey, Christopher G., additional, Vanhaesebroeck, Bart, additional, Stow, Jennifer L., additional, Arumugam, Thiruma V., additional, and Meunier, Frédéric A., additional

Published
2014
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6. PI3Kδ inhibition reduces TNF secretion and neuroinflammation in a mouse cerebral stroke model

Author

Low, Pei Ching, primary, Manzanero, Silvia, additional, Mohannak, Nika, additional, Narayana, Vinod K., additional, Nguyen, Tam H., additional, Kvaskoff, David, additional, Brennan, Faith H., additional, Ruitenberg, Marc J., additional, Gelderblom, Mathias, additional, Magnus, Tim, additional, Kim, Hyun Ah, additional, Broughton, Brad R. S., additional, Sobey, Christopher G., additional, Vanhaesebroeck, Bart, additional, Stow, Jennifer L., additional, Arumugam, Thiruma V., additional, and Meunier, Frédéric A., additional

Published
2014
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7. Phosphatidylinositol(4,5)bisphosphate coordinates actin-mediated mobilization and translocation of secretory vesicles to the plasma membrane of chromaffin cells

Author

Wen, Peter J., primary, Osborne, Shona L., additional, Zanin, Mark, additional, Low, Pei Ching, additional, Wang, Hai-Tao A., additional, Schoenwaelder, Simone M., additional, Jackson, Shaun P., additional, Wedlich-Söldner, Roland, additional, Vanhaesebroeck, Bart, additional, Keating, Damien J., additional, and Meunier, Frédéric A., additional

Published
2011
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10. Cytokine secretion in macrophages and other cells: pathways and mediators.

Author

Stow JL, Low PC, Offenhäuser C, and Sangermani D

Subjects
Animals, Cell Communication immunology, Endosomes, Humans, Immunity, Cellular, Secretory Pathway immunology, Secretory Vesicles, Cytokines metabolism, Macrophages immunology, Protein Transport
Abstract

Cytokines and other immune mediators are secreted by cells of the immune system during immune responses and as a means of communication. While the functions of these cytokines, chemokines and mediators are well known, the intracellular pathways that lead to their secretion by different cells are only now being fully documented. Cytokines in some cells are released from secretory granules while in other cells they are released via constitutive secretory pathways that instead have more dynamic vesicular carriers. Recent studies have revealed that newly synthesized cytokines can be routed via compartments such as recycling endosomes prior to their secretion. Here we describe and show examples of some of the pathways used for cytokine trafficking and release in macrophages, including some of the cellular machinery required for this transport. Increasingly, these trafficking pathways are revealed as having important regulatory roles in the execution of immune responses.

Published
2009
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