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Your search keyword '"Shaw, Andrey S"' showing total 578 results
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578 results on '"Shaw, Andrey S"'

156. Effects of CD2-associated protein deficiency on amyloid-β in neuroblastoma cells and in an APP transgenic mouse model.

Author

Fan Liao, Hong Jiang, Srivatsan, Subhashini, Qingli Xiao, Lefton, Katheryn B., Yamada, Kaoru, Mahan, Thomas E., Jin-Moo Lee, Shaw, Andrey S., and Holtzman, David M.

Subjects
AMYLOID genetics, AMYLOID beta-protein, ALZHEIMER'S disease, GLYCOPROTEINS, HYPOPROTEINEMIA
Abstract

Background: CD2-associated protein (CD2AP) is an SH3-containing scaffold adaptor protein which regulates the actin cytoskeleton. Recently, CD2AP was identified as a genetic risk factor for Alzheimer's disease (AD) by several genome-wide association studies. One of the hallmarks of AD is the accumulation of aggregated forms of Amyloid-β (Aβ) in the brain. In humans, CD2AP AD susceptibility locus (rs9349407) is associated with an increased plaque burden. Aβ production is highly regulated by endocytosis and is influenced by lysosomal function. Lysosomal trafficking is influenced by CD2AP. In this study, we decreased CD2AP levels in N2a neuroblastoma cultures and PS1APP mice and analyzed Aβ levels and plaque burden. Results: Our data show that suppressing CD2AP expression using shRNA in N2a-APP695 cells results in decreased cell membrane amyloid precursor protein, decreased Aβ release and a lower Aβ42/Aβ40 ratio. CD2AP protein is expressed in the brain as detected by western blot, and the expression level is dependent on gene dosage. In 1-month old PS1APP mice, complete loss of CD2AP in brain resulted in a decreased Aβ42/Aβ40 ratio in brain tissue lysates while there was no effect on Aβ deposition or accumulation in PS1APP mice expressing one copy of CD2AP. Conclusion: CD2-Associated Protein affects Aβ levels and Aβ42/Aβ40 ratio in vitro. The effect of CD2-Associated Protein on Aβ metabolism is subtle in vivo. [ABSTRACT FROM AUTHOR]

Published
2015
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157. Kinase Regulation by Hydrophobic Spine Assembly in Cancer.

Author

Jiancheng Hu, Ahuja, Lalima G., Meharena, Hiruy S., Kannan, Natarajan, Kornev, Alexandr P., Taylor, Susan S., and Shaw, Andrey S.

Subjects
PROTEIN kinases, CANCER genetics, CATALYSIS synthesis, GENETIC mutation, EPIDERMAL growth factor receptors
Abstract

new model of kinase regulation based on the assembly of hydrophobic spines has been proposed. Changes in their positions can explain the mechanism of kinase activation. Here, we examined mutations in human cancer for clues about the regulation of the hydrophobic spines by focusing initially on mutations to Phe. We identified a selected number of Phe mutations in a small group of kinases that included BRAF, ABL1, and the epidermal growth factor receptor. Testing some of these mutations in BRAF, we found that one of the mutations impaired ATP binding and catalytic activity but promoted noncatalytic allosteric functions. Other Phe mutations functioned to promote constitutive catalytic activity. One of these mutations revealed a previously underappreciated hydrophobic surface that functions to position the dynamic regulatory αC-helix. This supports the key role of the C-helix as a signal integration motif for coordinating multiple elements of the kinase to create an active conformation. The importance of the hydrophobic space around the αC-helix was further tested by studying a V600F mutant, which was constitutively active in the absence of the negative charge that is associated with the common V600E mutation. Many hydrophobic mutations strategically localized along the C-helix can thus drive kinase activation. [ABSTRACT FROM AUTHOR]

Published
2015
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165. Costimulation through NKG2D Enhances Murine CD8+ CTL Function: Similarities and Differences between NKG2D and CD28 Costimulation

Author

Markiewicz, Mary A., primary, Carayannopoulos, Leonidas N., additional, Naidenko, Olga V., additional, Matsui, Ken, additional, Burack, W. Richard, additional, Wise, Erica L., additional, Fremont, Daved H., additional, Allen, Paul M., additional, Yokoyama, Wayne M., additional, Colonna, Marco, additional, and Shaw, Andrey S., additional

Published
2005
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167. The c-SMAC

Author

Lin, Joseph, primary, Miller, Mark J., additional, and Shaw, Andrey S., additional

Published
2005
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173. Nephrin and CD2AP Associate with Phosphoinositide 3-OH Kinase and Stimulate AKT-Dependent Signaling

Author

Huber, Tobias B., primary, Hartleben, Björn, additional, Kim, Jeong, additional, Schmidts, Miriam, additional, Schermer, Bernhard, additional, Keil, Alexander, additional, Egger, Lotti, additional, Lecha, Rachel L., additional, Borner, Christoph, additional, Pavenstädt, Hermann, additional, Shaw, Andrey S., additional, Walz, Gerd, additional, and Benzing, Thomas, additional

Published
2003
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178. Kinase Suppressor of Ras (KSR) Is a Scaffold Which Facilitates Mitogen-Activated Protein Kinase Activation In Vivo

Author

Nguyen, AnhCo, primary, Burack, W. Richard, additional, Stock, Jeffrey L., additional, Kortum, Robert, additional, Chaika, Oleg V., additional, Afkarian, Maryam, additional, Muller, William J., additional, Murphy, Kenneth M., additional, Morrison, Deborah K., additional, Lewis, Robert E., additional, McNeish, John, additional, and Shaw, Andrey S., additional

Published
2002
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182. The immunological synapse and CD28-CD80 interactions

Author

Bromley, Shannon K., primary, Iaboni, Andrea, additional, Davis, Simon J., additional, Whitty, Adrian, additional, Green, Jonathan M., additional, Shaw, Andrey S., additional, Weiss, Arthur, additional, and Dustin, Michael L., additional

Published
2001
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186. The Immunological Synapse

Author

Bromley, Shannon K., primary, Burack, W. Richard, additional, Johnson, Kenneth G., additional, Somersalo, Kristina, additional, Sims, Tasha N., additional, Sumen, Cenk, additional, Davis, Mark M., additional, Shaw, Andrey S., additional, Allen, Paul M., additional, and Dustin, Michael L., additional

Published
2001
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193. Rac1 Activation in Podocytes Induces Rapid Foot Process Effacement and Proteinuria.

Author

Haiyang Yu, Suleiman, Hani, Kim, Alfred H. J., Miner, Jeffrey H., Dani, Adish, Shaw, Andrey S., and Akilesh, Shreeram

Subjects
KIDNEYS, KIDNEY glomerulus, KIDNEY tubules, TRANSGENES, LABORATORY mice, CYTOSKELETON
Abstract

The kidney's vital filtration function depends on the structural integrity of the glomerulus, the proximal portion of the nephron. Within the glomerulus, the architecturally complex podocyte forms the final cellular barrier to filtration. Injury to the podocyte results in a morphological change called foot process effacement, which is a ubiquitous feature of proteinuric diseases. The exact mechanism underlying foot process effacement is not known, but recently it has been proposed that this change might reflect activation of the Rac1 GTPase. To test this hypothesis, we generated a podocyte-specific, inducible transgenic mouse line that expressed constitutively active Rac1. When the Rac1 transgene was induced, we observed a rapid onset of proteinuria with focal foot process effacement. Using superresolution imaging, we verified that the induced transgene was expressed in damaged podocytes with altered foot process morphology. This work sheds new light on the complex balance of Rho GTPase signaling that is required for proper regulation of the podocyte cytoskeleton. [ABSTRACT FROM AUTHOR]

Published
2013
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