15 results on '"Barrow, Roxanne K."'
Search Results
2. RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1.
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Burnett, Patrick E., Barrow, Roxanne K., Cohen, Noam A., Snyder, Solomon H., and Sabatini, David M.
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PHOSPHORYLATION - Abstract
Focuses on the interaction of RAFT1 phosphorylation of the translational regulators p70 S6 Kinase and 4E-BP1. Examination of the RAFT1 function in the rapamycin-sensitive pathways; Information on its connection with downstream components of the pathway; Discussion on the links between three components of the rapaycin-sensitive signaling pathways.
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- 1998
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3. RACK1 binds to inositol 1,4,5-trisphosphate receptors and mediates Ca&sup+2; release.
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Patterson, Randen L., Van Rossum, Damian B., Barrow, Roxanne K., and Snyder, Solomon H.
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INOSITOL , *CALCIUM antagonists , *PROTEIN kinase C , *RNA , *BINDING sites , *PHOSPHATES - Abstract
RACK1 is not a G protein but closely resembles the heterotrimeric Gβ-subunit. RACK1 serves as a scaffold, linking protein kinase C to its substrates. We demonstrate that RACK1 physiologically binds inositol 1,4,5-trisphosphate receptors and regulates Ca2+ release by enhancing inositol 1,4,5-trisphosphate receptor binding affinity for inositol 1,4,5-trisphosphate. Overexpression of RACK1 or depletion of RACK1 by interference RNA markedly augments or diminishes Ca2+ release, respectively, without affecting Ca2+ entry. These findings establish RACK1 as a physiologic mediator of agonist-induced Ca2+ release. [ABSTRACT FROM AUTHOR]
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- 2004
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4. Rhes, a Physiologic Regulator of Sumoylation, Enhances Cross-sumoylation between the Basic Sumoylation Enzymes E1 and Ubc9.
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Subramaniam, Srinivasa, Mealer, Robert G., Sixt, Katherine M., Barrow, Roxanne K., Usiello, Alessandro, and Snyder, Solomon H.
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ENZYMES , *LIGASES , *CELL-mediated cytotoxicity , *LYSINE , *PROTEINS - Abstract
We recently reported that the small G-protein Rhes has the properties of a SUMO-E3 ligase and mediates mutant huntingtin (mHtt) cytotoxicity. We now demonstrate that Rhes is a physiologic regulator of sumoylation, which is markedly reduced in the corpus striatum of Rhes-deleted mice. Sumoylation involves activation and transfer of small ubiquitin-like modifier (SUMO) from the thioester of E1 to the thioester of Ubc9 (E2) and final transfer to lysines on target proteins, which is enhanced by E3s. We show that E1 transfers SUMO from its thioester directly to lysine residues on Ubc9, forming isopeptide linkages. Conversely, sumoylation on E1 requires transfer of SUMO from the thioester of Ubc9. Thus, the process regarded as "autosumoylation" reflects intermolecular transfer between E1 and Ubc9, which we designate "cross-sumoylation." Rhes binds directly to both E1 and Ubc9, enhancing cross-sumoylation as well as thioester transfer from E1 to Ubc9. [ABSTRACT FROM AUTHOR]
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- 2010
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5. Serine Racemase Deletion Protects Against Cerebral Ischemia and Excitotoxicity.
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Mustafa, Asif K., Ahmad, Abdullah S., Zeynalov, Emil, Gazi, Sadia K., Sikka, Gautam, Ehmsen, Jeffrey T., Barrow, Roxanne K., Coyle, Joseph T., Snyder, Solomon H., and Doré, Sylvain
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SERINE , *AMINO acids , *NITRIC oxide , *CEREBRAL arteries , *CEREBRAL ischemia , *NEUROTOXICOLOGY - Abstract
D-Serine, formed from L-serine by serine racemase (SR), is a physiologic coagonist atNMDAreceptors. Using mice with targeted deletion of SR, we demonstrate a role for D-serine inNMDAreceptor-mediated neurotoxicity and stroke. Brain cultures of SR-deleted mice display markedly diminished nitric oxide (NO) formation and neurotoxicity. In intact SR knock-out mice, NO formation and nitrosylation of NO targets are substantially reduced. Infarct volume following middle cerebral artery occlusion is dramatically diminished in several regions of the brains of SR mutant mice despite evidence of increased NMDA receptor number and sensitivity. [ABSTRACT FROM AUTHOR]
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- 2010
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6. Glutamatergic regulation of serine racemase via reversal of PIP2 inhibition.
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Mustafa, Asif K., van Rossum, Damian B., Patterso, Randen L., Maag, David, Ehmsen, Jeffrey T., Gazi, Sadia K., Chakraborty, Anutosh, Barrow, Roxanne K., Amzel, L. Mario, and Snyder, Solomon H.
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SERINE proteinases , *PROTEINASES , *AMINO acids , *GLUTAMIC acid , *PHOSPHOINOSITIDES - Abstract
D-serine is a physiologic coagonist with glutamate at NMDA-subtype glutamate receptors. As D-serine is localized in glia. synaptically released glutamate presumably stimulates the glia to form and release D-serine. enabling glutamate/D-serine cotrans-mission. We show that serine racemase (SR). which generates D-serine from L-serine, is physiologically inhibited by phosphatidylinositol (4,5)-bisphosphate (PIP2) presence in membranes where SR is localized. Activation of metabotropic glutamate receptors (mGluR5) on glia leads to phospholipase C-mediated degradation of PIP2, relieving SR inhibition. Thus mutants of SR that cannot bind PIP2 lose their membrane localizations and display a 4-fold enhancement of catalytic activity. Moreover, mGluR5 activation of SR activity is abolished by inhibiting phospholipase C. [ABSTRACT FROM AUTHOR]
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- 2009
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7. TRP_2, a Lipid/Trafficking Domain That Mediates Diacylglycerol-induced Vesicle Fusion.
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van Rossum, Damian B., Oberdick, Daniel, Rbaibi, Youssef, Bhardwaj, Gaurav, Barrow, Roxanne K., Nikolaidis, Nikolas, Snyder, Solomon H., Kiselyov, Kirill, and Patterson, Randen L.
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TRP channels , *MEMBRANE proteins , *LIPIDS , *BIOLOGICAL membranes , *CHANNELS (Structural members) - Abstract
We recently modeled transient receptor potential (TRP) channels using the Gestalt Domain Detection Algorithm-Basic Local Alignment Tool (GDDA-BLAST), which derives structural, functional, and evolutionary information from primary amino acid sequences using phylogenetic profiles (Ko, K. D., Hong, Y., Chang, G. S., Bhardwaj, G., van Rossum, D. B., and Patterson, R. L. (2008) Physics Arch. Quant. Methods arXiv:0806.2394v1). Herein we test our functional predictions for the TRP_2 domain of TRPC3; a domain of unknown function that is conserved in all TRPC channels. Our functional models of this domain identify both lipid binding and trafficking activities. In this study, we reveal: (i) a novel structural determinant of ion channel sensitivity to lipids, (ii) a molecular mechanism for the difference between diacylglycerol (DAG)-sensitive and DAG-insensitive TRPC subfamilies, and (iii) evidence that TRPC3 can comprise part of the vesicle fusion machinery. Indeed, the TRPC3 TRP_2 domain mediates channel trafficking to the plasma membrane and binds to plasma membrane lipids. Further, mutations in TRP_2, which alter lipid binding, also disrupt the DAG-mediated fusion of TRPC3-containing vesicles with the plasma membrane without disrupting SNARE interactions. Importantly, these data agree with the known role of DAG in membrane destabilization, which facilitates SNARE-dependent synaptic vesicle fusion (Villar, A. V., Goni, F. M., and Alonso, A. (2001) FEBS Lett. 494, 117-120 and Goni, F. M., and Alonso, A. (1999) Prog. Lipid Res. 38, 1-48). Taken together, functional models generated by GDDA-BLAST provide a computational platform for deriving domain functionality, which can have in vivo and mechanistic relevance. [ABSTRACT FROM AUTHOR]
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- 2008
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8. Modulation of d-Serine Levels in Brains of Mice Lacking PICK1
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Hikida, Takatoshi, Mustafa, Asif K., Maeda, Kazuhisa, Fujii, Kumiko, Barrow, Roxanne K., Saleh, Masoumeh, Huganir, Richard L., Snyder, Solomon H., Hashimoto, Kenji, and Sawa, Akira
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SERINE , *GENETICS , *ENZYMES , *SCHIZOPHRENIA , *BIPOLAR disorder , *CARRIER proteins , *WESTERN immunoblotting , *LABORATORY mice - Abstract
Background: d-serine is an endogenous coagonist of the N-methyl-d-aspartate subtype glutamate receptor. Genetic association studies have implicated genes coding for enzymes associated with d-serine metabolism in schizophrenia and bipolar disorder. Methods: Protein expression of serine racemase (SR) and its binding partner, protein interacting with C-kinase (PICK1), were examined by Western blotting in brains from wildtype and PICK1 knockout mice. Levels of d-serine in wildtype and PICK1 mice were also examined by an established high-pressure liquid chromatography protocol. Results: Expression of SR and PICK1 proteins was developmentally regulated. Although no change was observed in the level of SR protein, levels of d-serine were selectively decreased in the forebrain of neonatal PICK1 knockout mice, compared with those in wildtype mice. Conclusions: PICK1 may be involved in the regulation of brain d-serine levels and SR in a spatially and temporally specific manner. [Copyright &y& Elsevier]
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- 2008
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9. Nitric oxide S-nitrosylates serine racemase, mediating feedback inhibition of D-serine formation.
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Mustafa, Asif K., Kumar, Manish, Selvakumar, Balakrishnan, Ho, Gary P. H., Ehmsen, Jeffrey T., Barrow, Roxanne K., Amzel, L. Mario, and Snyder, Solomon H.
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SERINE , *AMINO acids , *METHYL aspartate , *ADENOSINE triphosphate , *NITRIC-oxide synthases - Abstract
Serine racemase (SR) generates D-serine, a coagonist with glutamate at NMDA receptors. We show that SR is physiologically S-nitrosylated leading to marked inhibition of enzyme activity. Inhibition involves interactions with the cofactor ATP reflecting juxtaposition of the ATP-binding site and cysteine-113 (C113), the site for physiological S-nitrosylation. NMDA receptor physiologically enhances SR 5-nitrosylation by activating neuronal nitric-oxide synthase (nNOS) . These findings support a model whereby postsynaptic stimulation of nitric-oxide (NO) formation feeds back to presynaptic cells to S-nitrosylate SR and decrease D-serine availability to postsynaptic NMDA receptors. [ABSTRACT FROM AUTHOR]
- Published
- 2007
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10. DANGER, a Novel Regulatory Protein of Inositol 1 ,4,5-Trisphosphate-Receptor Activity*.
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Van Rossum, Damian B., Patterson, Randen L., King-Ho Cheung, Barrow, Roxanne K., Syrovatkina, Viktoriya, Gessell, Gregory S., Burkholder, Scott G., Watkins, D. Neil, Foskett, J. Kevin, and Snyder!, Solomon H.
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INOSITOL , *PROTEINS , *CELL lines , *PHOSPHATES , *ALCOHOLS (Chemical class) , *SUGARS - Abstract
We report the cloning and characterization of DANGER, a novel protein which physiologically binds to inositol 1,4,5-trisphosphate receptors (IP3R). DANGER is a membrane-associated protein predicted to contain a partial MAB-21 domain. It is expressed in a wide variety of neuronal cell lineages where it localizes to membranes in the cell periphery together with IP3R. DANGER interacts with IP3R in vitro and co-immunoprecipitates with IP3R from cellular preparations. DANGER robustly enhances Ca2+-mediated inhibition of IP3R Ca2+ release without affecting IP3 binding in microsomal assays and inhibits gating in single-channel recordings of IP3R. DANGER appears to allosterically modulate the sensitivity of IP3R to Ca2+ inhibition, which likely alters IP3R-mediated Ca2+ dynamics in cells where DANGER and IP3R are co-expressed. [ABSTRACT FROM AUTHOR]
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- 2006
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11. Phospholipase C?1 controls surface expression of TRPC3 through an intermolecular PH domain.
- Author
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van Rossum, Damian B., Patterson, Randen L., Sharma, Sumit, Barrow, Roxanne K., Kornberg, Michael, Gill, Donald L., and Snyder, Solomon H.
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PHOSPHOLIPASES , *ION channels , *HYDROGEN-ion concentration , *PROTEINS , *BIOCHEMISTRY - Abstract
Many ion channels are regulated by lipids, but prominent motifs for lipid binding have not been identified in most ion channels. Recently, we reported that phospholipase C?1 (PLC-?1) binds to and regulates TRPC3 channels, components of agonist-induced Ca2+ entry into cells. This interaction requires a domain in PLC-?1 that includes a partial pleckstrin homology (PH) domain-a consensus lipid-binding and protein-binding sequence. We have developed a gestalt algorithm to detect hitherto‘invisible’PH and PH-like domains, and now report that the partial PH domain of PLC-?1 interacts with a complementary partial PH-like domain in TRPC3 to elicit lipid binding and cell-surface expression of TRPC3. Our findings imply a far greater abundance of PH domains than previously appreciated, and suggest that intermolecular PH-like domains represent a widespread signalling mode. [ABSTRACT FROM AUTHOR]
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- 2005
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12. Serine racemase: Activation by glutamate neurotransmission via glutamate receptor interacting protein and mediation of neuronal migration.
- Author
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Kim, Paul M., Aizawa, Hiroyuki, Kim, Peter S., Huang, Alex S., Wickramasinghe, Sasrutha R., Kashani, Amir H., Barrow, Roxanne K., Huganir, Richard L., Ghosh, Anirvan, and Snyder, Solomon H.
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NEURAL transmission , *SERINE , *AMINO acids , *SYNAPSES , *CELL migration , *CEREBELLUM - Abstract
Serine racemase (SR), localized to astrocytic glia that ensheathe synapses, converts L-serine to D-serine, an endogenous ligand of the NMDA receptor. We report the activation of SR by glutamate neurotransmission involving α-amino-3-hydroxy-5-methyljsoxazole-4-propionic acid receptors via glutamate receptor interacting protein (GRIP) and the physiologic regulation of cerebellar granule cell migration by SR. GRIP physiologically binds SR, augmenting SR activity and D-serine release. GRIP infection of neonatal mouse cerebellum in vivo enhances granule cell migration. Selective degradation of D-serine by D-amino acid oxidase and pharmacologic inhibition of SR impede migration, whereas D-serine activates the process. Thus, in neuronal migration, glutamate stimulates Bergmann glia to form and release D-serine, Which, together with glutamate, activates NMDA receptors on granule neurons, chemo-kinetically enhancing migration. [ABSTRACT FROM AUTHOR]
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- 2005
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13. Agonist-induced Ca²+; entry determined by inositol 1,4,5-trisphosphate recognition.
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Van Rossum, Damian B., Patterson, Randen L., Kiselyov, Kirill, Boehning, Darren, Barrow, Roxanne K., Gill, Donald L., and Snyder, Solomon H.
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CALCIUM antagonists , *INOSITOL phosphates , *B cells , *CELL receptors , *BINDING sites , *CELL membranes - Abstract
It has been considered that Ca2+ release is the causal trigger for Ca2+ entry after receptor activation. In DT40 B cells devoid of inositol 1,4,5-trisphosphate receptors (IP3R), the lack of Ca2+ entry in response to receptor activation is attributed to the absence of Ca2+ release. We reveal in this article that IP3R recognition of IP3 determines agonist-induced Ca2+ entry (ACE), independent of its Ca2+ release activity. In DT40 IP3R-/- cells, endogenous ACE can be rescued with type 1 IP3R mutants (both a ΔC-terminal truncation mutant and a D2550A pore mutant), which are defective in Ca2+ release channel activity. Thus, in response to B cell receptor activation, ACE is restored in an IP3R-dependent manner without Ca2+ store release. Conversely, ACE cannot be rescued with mutant IP3Rs lacking IP3 binding (both the Δ90-110 and R265Q IP3-binding site mutants). We conclude that an IP3-dependent conformational change in the IP3R, not endoplasmic reticulum Ca2+ pool release, triggers ACE. [ABSTRACT FROM AUTHOR]
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- 2004
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14. Haem oxygenase-1 prevents cell death by regulating cellular iron.
- Author
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Ferris, Christopher D., Jaffrey, Samie R., Sawa, Akira, Takahashi, Masaaki, Brady, Stephen D., Barrow, Roxanne K., Tysoe, Steven A., Wolosker, Herman, Barañano, David E., Doré, Sylvain, Poss, Kenneth D., and Snyder, Solomon H.
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HEME oxygenase , *CELL death , *IRON in the body - Abstract
Haem oxygenase-1 (HO1) is a heat-shock protein that is induced by stressful stimuli. Here we demonstrate a cytoprotective role for HO1: cell death produced by serum deprivation, staurosporine or etoposide is markedly accentuated in cells from mice with a targeted deletion of the HO1 gene, and greatly reduced in cells that overexpress HO1. Iron efflux from cells is augmented by HO1 transfection and reduced in HO1-deficient fibroblasts. Iron accumulation in HO1-deficient cells explains their death: iron chelators protect HO1-deficient fibroblasts from cell death. Thus, cytoprotection by HO1 is attributable to its augmentation of iron efflux, reflecting a role for HO1 in modulating intracellular iron levels and regulating cell viability. [ABSTRACT FROM AUTHOR]
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- 1999
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15. Inositol 1,4, 5-trisphosphate receptor/GAPDH complex augments Ca2+ release via locally derived NADH.
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Patterson, Randen L., van Rossum, Damian B., Kaplin, Adam I., Barrow, Roxanne K., and Snyder, Solomon H.
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INOSITOL , *CALCIUM , *ALCOHOLS (Chemical class) , *VITAMIN B complex , *CELLS , *BIOENERGETICS - Abstract
NADH regulates the release of calcium from the endoplasmic reticulum by modulation of inositol 1,4,5-trisphosphate receptors (IP3R), accounting for the augmented calcium release of hypoxic cells. We report selective binding of IP3R to GAPDH, whose activity leads to the local generation of NADH to regulate intracellular calcium signaling. This interaction requires cysteines 992 and 995 of IP3R and C150 of GAPDH. Addition of native GAPDH and NAD+ to WT IP3R stimulates calcium release, whereas no stimulation occurs with C992S/995S IP3R that cannot bind GAPDH. Thus, the IP3R/ GAPDH interaction likely enables cellular energy dynamics to impact calcium signaling. [ABSTRACT FROM AUTHOR]
- Published
- 2005
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