Research Topics
Genomes and Genes
| John D ScottSummaryAffiliation: University of Washington Country: USA Publications
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Publications
Cell signaling in space and time: where proteins come together and when they're apartJohn D Scott
Department of Pharmacology, Howard Hughes Medical Institute, Box 357750, University of Washington School of Medicine, Seattle, WA 98195, USA
Science 326:1220-4. 2009..This requires that the activators, effectors, enzymes, and substrates that respond to cellular signals come together when they need to...- Shedding light on local kinase activationJohn D Scott
Howard Hughes Medical Institute, Department of Pharmacology, University of Washington School of Medicine, 1959 Pacific Ave, NE, Seattle, WA 98195 USA
BMC Biol 10:61. 2012..We discuss here how biosensors are being used to decode this language, affording an unprecedented glimpse into spatio-temporal patterns of protein phosphorylation events within the cell... - Anchored phosphatases modulate glucose homeostasisSimon A Hinke
Department of Pharmacology, Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA
EMBO J 31:3991-4004. 2012..Thus anchored signalling events that facilitate insulin secretion and glucose homeostasis may be set by AKAP150 associated phosphatase activity... - AKAP-Lbc mobilizes a cardiac hypertrophy signaling pathwayGraeme K Carnegie
Howard Hughes Medical Institute, Vollum Institute, Oregon Health and Science University, Portland, OR 97239, USA
Mol Cell 32:169-79. 2008..These studies uncover a role for AKAP-Lbc in which increased expression of the anchoring protein selectively amplifies a signaling pathway that drives cardiac myocytes toward a pathophysiological outcome... 
Role for A kinase-anchoring proteins (AKAPS) in glutamate receptor trafficking and long term synaptic depressionEric M Snyder
Howard Hughes Medical Institute, The Picower Center for Learning and Memory and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
J Biol Chem 280:16962-8. 2005..These data indicate that synaptic anchoring of PKA through association with AKAPs plays an important role in the regulation of AMPA receptor surface expression and synaptic plasticity...- Ubiquitination regulates PSD-95 degradation and AMPA receptor surface expressionMarcie Colledge
Howard Hughes Medical Institute, Vollum Institute, Oregon Health and Science University, Portland, OR 97239, USA
Neuron 40:595-607. 2003..These data suggest that ubiquitination of PSD-95 through an Mdm2-mediated pathway is critical in regulating AMPA receptor surface expression during synaptic plasticity... - AKAP-Lbc nucleates a protein kinase D activation scaffoldGraeme K Carnegie
Howard Hughes Medical Institute, Vollum Institute, Oregon Health and Sciences University, Portland, OR 97239, USA
Mol Cell 15:889-99. 2004..This configuration illustrates the utility of kinase anchoring as a mechanism to constrain the action of broad-spectrum enzymes... - Loss of AKAP150 perturbs distinct neuronal processes in miceBrian J Tunquist
Howard Hughes Medical Institute, Oregon Health and Science University, 3181 South West Sam Jackson Park Road, Portland, Oregon 97239, USA
Proc Natl Acad Sci U S A 105:12557-62. 2008..These studies argue that distinct AKAP150-enzyme complexes regulate context-dependent neuronal signaling events in vivo... - Bioinformatic design of A-kinase anchoring protein-in silico: a potent and selective peptide antagonist of type II protein kinase A anchoringNeal M Alto
Howard Hughes Medical Institute, Vollum Institute, Oregon Health and Science University, Portland OR 97239, USA
Proc Natl Acad Sci U S A 100:4445-50. 2003..Thus, computer-based and peptide array screening approaches have generated a reagent that binds PKA with higher affinity than previously described AKAPs... - Dynamic regulation of cAMP synthesis through anchored PKA-adenylyl cyclase V/VI complexesAndrea L Bauman
Howard Hughes Medical Institute, Vollum Institute, L 474, Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, Portland, Oregon 97239, USA
Mol Cell 23:925-31. 2006..This protein configuration permits the formation of a negative feedback loop that temporally regulates cAMP production... - Restoration of normal L-type Ca2+ channel function during Timothy syndrome by ablation of an anchoring proteinEdward P Cheng
Department of Physiology and Biophysics, University of Washington, 1705 NE Pacific Street, Seattle, WA 98195, USA
Circ Res 109:255-61. 2011..2 channels causes long QT syndrome 8 (LQT8), a disease also known as Timothy syndrome. However, the mechanisms by which this mutation enhances Ca(V)1.2-LQT8 currents and generates lethal arrhythmias are unclear... - AKAP79-mediated targeting of the cyclic AMP-dependent protein kinase to the beta1-adrenergic receptor promotes recycling and functional resensitization of the receptorLidia A Gardner
Department of Pharmacology, University of Tennessee Health Sciences Center, Memphis, Tennessee 38163, USA
J Biol Chem 281:33537-53. 2006..Thus, AKAP79 provides PKA to phosphorylate the beta(1)-AR and thereby dictate the recycling and resensitization itineraries of the beta(1)-AR... - Increased coupled gating of L-type Ca2+ channels during hypertension and Timothy syndromeManuel F Navedo
Department of Physiology and Biophysics, University of Washington Seattle, 1705 NE Pacific Street, Seattle, WA 98195, USA
Circ Res 106:748-56. 2010..L-Type (Cav1.2) Ca(2+) channels are critical regulators of muscle and neural function. Although Cav1.2 channel activity varies regionally, little is known about the mechanisms underlying this heterogeneity... - AKAP220 protein organizes signaling elements that impact cell migrationJeremy S Logue
Howard Hughes Medical Institute, University of Washington School of Medicine, Seattle, Washington 98195, USA
J Biol Chem 286:39269-81. 2011..This reveals an unappreciated role for this anchored kinase/microtubule effector protein network in the propagation of cell motility... - A WAVE-1 and WRP signaling complex regulates spine density, synaptic plasticity, and memoryScott H Soderling
Howard Hughes Medical Institute, Oregon Health and Science University, Portland, Oregon 97239, USA
J Neurosci 27:355-65. 2007..This implies that signaling through WAVE-1 complexes is essential for neural plasticity and cognitive behavior... - Interaction with AKAP79 modifies the cellular pharmacology of PKCNaoto Hoshi
Department of Pharmacology, 360 Med Surge II, University of California, Irvine, Irvine, CA 92697, USA
Mol Cell 37:541-50. 2010..This implies that intracellular binding partners not only couple individual molecular events in a cell signaling process but can also change the pharmacological profile of certain protein kinases... - Association of an A-kinase-anchoring protein signaling scaffold with cadherin adhesion molecules in neurons and epithelial cellsJessica A Gorski
Department of Pharmacology, University of Colorado at Denver and Health Sciences Center, Aurora, CO 80045, USA
Mol Biol Cell 16:3574-90. 2005..This neuronal regulation of AKAP79/150 targeting to cadherins may be important in functional and structural synaptic modifications underlying plasticity... - AKAP2 anchors PKA with aquaporin-0 to support ocular lens transparencyMatthew G Gold
Department of Pharmacology, Howard Hughes Medical Institute, University of Washington School of Medicine, Seattle, WA, USA
EMBO Mol Med 4:15-26. 2012..Thus, anchored PKA modulation of AQP0 is a homeostatic mechanism that must be physically intact to preserve lens transparency... - AKAP-Lbc enhances cyclic AMP control of the ERK1/2 cascadeF Donelson Smith
Howard Hughes Medical Institute, Department of Pharmacology, University of Washington School of Medicine, 1959 Pacific Avenue NE, Seattle, WA 98195, USA
Nat Cell Biol 12:1242-9. 2010..This offers mechanistic insight into cAMP-responsive control of ERK signalling events... - An entirely specific type I A-kinase anchoring protein that can sequester two molecules of protein kinase A at mitochondriaChristopher K Means
Department of Pharmacology, Howard Hughes Medical Institute, University of Washington School of Medicine, 1959 Pacific Avenue NE, Seattle, WA 98195, USA
Proc Natl Acad Sci U S A 108:E1227-35. 2011..Imaging, proteomic analysis, and subcellular fractionation experiments reveal that SKIP is enriched at the inner mitochondrial membrane where it associates with a prominent PKA substrate, the coiled-coil helix protein ChChd3... - Distinct enzyme combinations in AKAP signalling complexes permit functional diversityNaoto Hoshi
Howard Hughes Medical Institute, Vollum Institute, Oregon Health and Science University, 3181 S W Sam Jackson Park Road, Portland, OR 97239, USA
Nat Cell Biol 7:1066-73. 2005..Utilization of distinct enzyme combinations in this manner provides a means to expand the repertoire of cellular events that the same AKAP modulates... - Anchored protein kinase A recruitment of active Rac GTPaseJeremy S Logue
Howard Hughes Medical Institute, University of Washington School of Medicine, Seattle, Washington 98195, USA
J Biol Chem 286:22113-21. 2011..These findings imply that IQGAP2 and AKAP220 act synergistically to sustain PKA-mediated recruitment of effectors such as Rac GTPases that impact the actin cytoskeleton... - Coordinated signal integration at the M-type potassium channel upon muscarinic stimulationAnastasia Kosenko
Department of Pharmacology, University of California, Irvine, CA 92697, USA
EMBO J 31:3147-56. 2012..This pathway enhances the effect of concomitant reduction of PIP2, which leads to disruption of the M-channel function. These findings clarify how a common lipid cofactor, such as PIP2, can selectively regulate ion channels... - AKAP signaling complexes: getting to the heart of the matterGeorge McConnachie
Howard Hughes Medical Institute, Vollum Institute, L-474, Oregon Health and Science University, 3181 S.W. Sam Jackson Park Road, Portland, OR 97239, USA
Trends Mol Med 12:317-23. 2006..These are only two examples of how AKAPs contribute to specificity in cAMP signaling. This review will explore recent development that illustrates the role of multiprotein complexes in the regulation of cAMP signaling... - Contextual utilization of enzymes in discrete AKAP79/150 signalling complexesNaoto Hoshi
Howard Hughes Medical Institute, Vollum Institute, Oregon Health and Science University, 3181 S W Sam Jackson Park Road, Portland, OR 97239, USA
Eur J Cell Biol 85:621-2. 2006..Utilization of distinct enzyme combinations in this manner provides a means to expand the repertoire of cellular events that the same AKAP modulates... - Gravin is a transitory effector of polo-like kinase 1 during cell divisionDavid A Canton
Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA
Mol Cell 48:547-59. 2012..In situ detection of phospho-T766 Gravin in biopsy sections of human glioblastomas suggests that this phosphorylation event might identify malignant neoplasms... - MyRIP anchors protein kinase A to the exocyst complexApril S Goehring
Howard Hughes Medical Institute, Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA
J Biol Chem 282:33155-67. 2007..These data indicate that MyRIP functions as a scaffolding protein that links PKA to components of the exocytosis machinery... - A-kinase anchoring proteins: from protein complexes to physiology and diseaseGraeme K Carnegie
Department of Pharmacology, Howard Hughes Medical Institute, University of Washington, School of Medicine, Seattle, Washington 98195, USA
IUBMB Life 61:394-406. 2009..These anchoring proteins form multi-protein complexes that integrate cAMP signaling with other pathways and signaling events. In this review, we focus on recent advances in the elucidation of AKAP function... - Orchestration of synaptic plasticity through AKAP signaling complexesAndrea L Bauman
Howard Hughes Medical Institute, Vollum Institute, Oregon Health and Science University, Portland, OR 97239, USA
Neuropharmacology 46:299-310. 2004..In this review we will focus on the role of PKA in synaptic plasticity and discuss how the compartmentalization of PKA through its association with A-Kinase Anchoring Proteins (AKAPs) affect PKA function in this process... - Cardiomyocytes from AKAP7 knockout mice respond normally to adrenergic stimulationBrian W Jones
Department of Pharmacology, University of Washington, Seattle, WA 98195, USA
Proc Natl Acad Sci U S A 109:17099-104. 2012..Immunoblot and RT-PCR revealed that only the long isoforms of AKAP7 were detectable in ventricular cardiomyocytes. The results indicate that AKAP7 is not required for regulation of Ca(2+) handling in mouse cardiomyocytes... - PP2B/calcineurin-mediated desensitization of TRPV1 does not require AKAP150Elaine D Por
Department of Pharmacology, Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229 3900, USA
Biochem J 432:549-56. 2010..These findings allow us to conclude that pharmacological desensitization of TRPV1 by PP2B may involve additional regulatory components... - Organizing signal transduction through A-kinase anchoring proteins (AKAPs)Jeremy S Logue
Howard Hughes Medical Institute and Department of Pharmacology, University of Washington School of Medicine, Seattle, WA 98195, USA
FEBS J 277:4370-5. 2010..Selected A-kinase anchoring protein signaling complexes are highlighted in this minireview... - A-kinase anchoring proteins and neuronal signaling mechanismsGraeme K Carnegie
Howard Hughes Medical Institute, Vollum Institute, Oregon Health and Sciences University, Portland, Oregon 97201, USA
Genes Dev 17:1557-68. 2003 - Architecture and dynamics of an A-kinase anchoring protein 79 (AKAP79) signaling complexMatthew G Gold
Howard Hughes Medical Institute, Department of Pharmacology, University of Washington School of Medicine, 1959 Pacific Avenue NE, Seattle, WA 98195, USA
Proc Natl Acad Sci U S A 108:6426-31. 2011..This leads to activation of the anchored phosphatases. Our architectural model reveals how dimeric AKAP79 concentrates pockets of second messenger responsive enzyme activities at the plasma membrane... - Discovery of cellular substrates for protein kinase A using a peptide array screening protocolF Donelson Smith
Howard Hughes Medical Institute, Department of Pharmacology, University of Washington School of Medicine, 1959 Pacific Avenue NE, Seattle, WA 98195, USA
Biochem J 438:103-10. 2011.... - Mapping the protein phosphatase-2B anchoring site on AKAP79. Binding and inhibition of phosphatase activity are mediated by residues 315-360Kimberly L Dodge
Howard Hughes Medical Institute, Oregon Health Sciences University, Portland 97201, USA
J Biol Chem 277:48796-802. 2002..We propose that the structural features of this AKAP79-PP2B-binding domain may share similarities with other proteins that serve to coordinate PP2B localization and activity... - Intracellular targeting of protein kinases and phosphatasesNeal Alto
Howard Hughes Medical Institute, Vollum Institute, Portland, Oregon 97201 3098, USA
Diabetes 51:S385-8. 2002.... - A-kinase anchoring proteins take shapeDarren L Beene
Howard Hughes Medical Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA
Curr Opin Cell Biol 19:192-8. 2007..For example, molecular and genetic approaches have been used to show that the neuronal anchoring protein WAVE1 integrates signaling from PKA and Cdk5 to regulate actin polymerization and cytoskeletal events... - Calcineurin anchoring and cell signalingKimberly L Dodge
Howard Hughes Medical Institute, Vollum Institute, Oregon Health and Sciences University, Portland, OR, USA
Biochem Biophys Res Commun 311:1111-5. 2003..This review emphasizes how the targeting of calcineurin through interaction with various anchoring proteins facilitates phosphatase regulation of T-cell activation, neuronal excitability and cardiac hypertrophy... - The protein kinase A anchoring protein mAKAP coordinates two integrated cAMP effector pathwaysKimberly L Dodge-Kafka
Howard Hughes Medical Institute, Oregon Health and Sciences University, Portland, Oregon 97239, USA
Nature 437:574-8. 2005..Thus, two coupled cAMP-dependent feedback loops are coordinated within the context of the mAKAP complex, suggesting that local control of cAMP signalling by AKAP proteins is more intricate than previously appreciated... - The where's and when's of kinase anchoringF Donelson Smith
Howard Hughes Medical Institute, Vollum Institute, Oregon Health and Sciences University, MRB322, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA
Trends Biochem Sci 31:316-23. 2006.... - Regulation of GluR1 by the A-kinase anchoring protein 79 (AKAP79) signaling complex shares properties with long-term depressionSteven J Tavalin
Howard Hughes Medical Institute, Vollum Institute, Oregon Health Sciences University, Portland, Oregon 97201, USA
J Neurosci 22:3044-51. 2002..Thus, the integration of intracellular signals relevant for LTD may be transduced to GluR1 by the AKAP79 signaling complex... - Loss of WAVE-1 causes sensorimotor retardation and reduced learning and memory in miceScott H Soderling
Howard Hughes Medical Institute, Vollum Institute, Oregon Health and Science University, Portland, OR 97239, USA
Proc Natl Acad Sci U S A 100:1723-8. 2003..Thus WAVE-1 is required for normal neural functioning... - Influenza A pneumonia presenting as progressive focal infiltrates in a stem cell transplant recipientJohn D Scott
Department of Medicine, University of Washington, Harborview Medical Center, 325 Ninth Avenue, Box 359938, Seattle, WA 98104 2499, USA
J Clin Virol 31:96-9. 2004..Stem cell transplant recipients are susceptible to pulmonary infections, including influenza A. Typically, isolated influenza pneumonia has a diffuse, interstitial infiltrate pattern... - Role of combination therapy in chronic hepatitis BJohn D Scott
Harborview Medical Center, 325 Ninth Avenue, Box 359938, Seattle, WA 98104, USA
Curr Gastroenterol Rep 11:28-36. 2009.... 
Diagnosis of depression in former injection drug users with chronic hepatitis CJohn D Scott
Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA 98104, USA
J Clin Gastroenterol 45:462-7. 2011..This study seeks to define the performance characteristics of 2 common depression screening tests and how psychiatric diagnoses affect adherence to treatment...- Chronic liver disease in Aboriginal North AmericansJohn D Scott
Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Harborview Medical Center, 325 Ninth Avenue, Seattle, WA 98144, USA
World J Gastroenterol 14:4607-15. 2008..In addition, more research is needed on the treatment of hepatitis C virus (HCV) infection and non-alcoholic fatty liver disease (NAFLD) in this population... - High rate of spontaneous negativity for hepatitis C virus RNA after establishment of chronic infection in Alaska NativesJohn D Scott
Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA
Clin Infect Dis 42:945-52. 2006..Hepatitis C virus (HCV) leads to chronic infection in 70%-85% of exposed patients. Spontaneous clearance of the virus after chronic infection is believed to occur rarely... - Hepatitis C virus is infrequently evaluated and treated in an urban HIV clinic populationJohn D Scott
Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA
AIDS Patient Care STDS 23:925-9. 2009..Further efforts to identify and to overcome barriers to HCV treatment are warranted... - Kinase- and phosphatase-anchoring proteins: harnessing the dynamic duoAndrea L Bauman
Howard Hughes Medical Institute, Vollum Institute, Oregon Health and Sciences University, 3181 S.W. Sam Jackson Park Road, Portland, OR 97201-3098, USA
Nat Cell Biol 4:E203-6. 2002 - A-kinase-anchoring proteinsLorene K Langeberg
Howard Hughes Medical Institute, Vollum Institute, Oregon Health and Sciences University, Portland, OR 97239, USA
J Cell Sci 118:3217-20. 2005 - The WRP component of the WAVE-1 complex attenuates Rac-mediated signallingScott H Soderling
Howard Hughes Medical Institute, Vollum Institute, 3181 Sam Jackson Park Road, Portland, Oregon 97239 3098, USA
Nat Cell Biol 4:970-5. 2002..WRP binds directly to WAVE-1 through its Src homology domain 3 and specifically inhibits Rac function in vivo. Thus, we propose that WRP is a binding partner of WAVE-1 that functions as a signal termination factor for Rac... - Rab32 is an A-kinase anchoring protein and participates in mitochondrial dynamicsNeal M Alto
Howard Hughes Medical Institute, Vollum Institute, Oregon Health and Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97201, USA
J Cell Biol 158:659-68. 2002..This implicates Rab32 as a participant in synchronization of mitochondrial fission. Thus, Rab32 is a dual function protein that participates in both mitochondrial anchoring of PKA and mitochondrial dynamics... - Signaling complexes: junctions on the intracellular information super highwayF Donelson Smith
Howard Hughes Medical Institute, Vollum Institute, Oregon Health and Sciences University, 3181 S.W. Sam Jackson Park Road, Portland, Oregon 97201-3098, USA
Curr Biol 12:R32-40. 2002..A major objective of the signaling community is to ascertain how signals flow through compartmentalized transduction units that contain transmembrane receptors, protein kinases, phosphatases and their substrates... - Signal integration through blending, bolstering and bifurcating of intracellular informationCatherine T Pawson
Howard Hughes Medical Institute, Department of Pharmacology, University of Washington, School of Medicine, Seattle, Washington, USA
Nat Struct Mol Biol 17:653-8. 2010..The ability to organize these enzymes into multiprotein complexes allows for a high degree of fidelity, efficiency and spatial precision in signaling responses... - Creating order from chaos: cellular regulation by kinase anchoringJohn D Scott
Howard Hughes Medical Institute and Department of Pharmacology, University of Washington School of Medicine, Seattle, Washington 98195, USA
Annu Rev Pharmacol Toxicol 53:187-210. 2013.... - AKAP mediated signal transductionJennifer J Carlisle Michel
Howard Hughes Medical Institute, Vollum Institute, Portland, Oregon 97201 3098, USA
Annu Rev Pharmacol Toxicol 42:235-57. 2002..This review details the most recent advances in our understanding of the various biological functions dependent upon AKAP-anchored signaling complexes... - Networking with AKAPs: context-dependent regulation of anchored enzymesEmily J Welch
Howard Hughes Medical Institute, Department of Pharmacology, University of Washington School of Medicine, Seattle, WA 98195, USA
Mol Interv 10:86-97. 2010..This article charts the inception of the PKA-anchoring hypothesis, the characterization of AKAPs and their nomenclature, and the physiological roles of context-specific AKAP signaling complexes... - Alpha-dystrobrevin-1 recruits alpha-catulin to the alpha1D-adrenergic receptor/dystrophin-associated protein complex signalosomeJohn S Lyssand
Department of Pharmacology and Physiology and Biophysics, University of Washington, Seattle, WA 98195, USA
Proc Natl Acad Sci U S A 107:21854-9. 2010..Taken together, our study implicates α-catulin as a unique regulator of GPCR signaling and represents a unique expansion of the intricate and continually evolving array of GPCR signaling networks...
Research Grants
- Anchored Kinase Signaling Mechanisms in Cardiac HypertrophyJohn D Scott; Fiscal Year: 2010....
- MOLECULAR ANALYSIS OF ANCHORING PROTEINSJohn Scott; Fiscal Year: 2003....
- MOLECULAR ANALYSIS OF PKA-ANCHORING PROTEIN INTERACTIONJohn Scott; Fiscal Year: 1993..Therefore, specific aim 2 will use recombinant RIalpha as a probe to screen a pituitary cDNA expression library to isolate clones to this RI-anchoring protein...
- MOLECULAR ANALYSIS OF ANCHORING PROTEINSJohn Scott; Fiscal Year: 1999....
- Anchored Kinase Signaling Mechanisms in Cardiac HypertrophyJohn D Scott; Fiscal Year: 2010....