Joseph BeavoSummaryAffiliation: University of Washington Country: USA Publications
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Publications
cAMP-specific phosphodiesterases 8A and 8B, essential regulators of Leydig cell steroidogenesisMasami Shimizu-Albergine
Department of Pharmacology, University of Washington, Seattle, Washington 98195 7280, USA
Mol Pharmacol 81:556-66. 2012..They also suggest that in order for PDE inhibitor therapy to be an effective stimulator of steroidogenesis, both PDE8 isozymes and PDE4 need to be simultaneously targeted...
Cyclic nucleotide research -- still expanding after half a centuryJoseph A Beavo
Department of Pharmacology, University of Washington, Seattle, Washington 98195 7280, USA
Nat Rev Mol Cell Biol 3:710-8. 2002..The breadth and impact of this work is reflected by five different Nobel prizes...- Crystal structure of the tandem GAF domains from a cyanobacterial adenylyl cyclase: modes of ligand binding and dimerizationSergio E Martinez
Department of Pharmacology, University of Washington, Seattle, WA 98195, USA
Proc Natl Acad Sci U S A 102:3082-7. 2005..Finally, a conserved asparagine appears to be a new addition to the signature NKFDE motif, and a mechanism for this motif to stabilize the cNMP-binding pocket is proposed... - Trypanosome cyclic nucleotide phosphodiesterase 2B binds cAMP through its GAF-A domainSunil Laxman
Department of Pharmacology, University of Washington, Seattle, Washington 98195-7280, USA
J Biol Chem 280:3771-9. 2005..These properties of the GAF-A domain of TbPDE2B thus suggest that it could be a new target for anti-trypanosomal drugs... 
Cyclic nucleotide signaling mechanisms in trypanosomes: possible targets for therapeutic agentsSunil Laxman
Department of Pharmacology, University of Washington School of Medicine, Seattle, WA 98105, USA
Mol Interv 7:203-15. 2007..In this review, we discuss recent developments, emerging ideas, and gaps in knowledge in this area of research, highlighting aspects of enzymes in the cAMP signaling pathway that may be good targets for antitrypanosomal drug therapy...- Molecular determinants for cyclic nucleotide binding to the regulatory domains of phosphodiesterase 2AAlbert Y Wu
Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA
J Biol Chem 279:37928-38. 2004..This high affinity suggests that cGMP binding to PDE2 GAF-B activates the enzyme rapidly, stoichiometrically, and in an all or none fashion, rather than variably over a large range of cyclic nucleotide concentrations... - Cyclic nucleotides promote monocyte differentiation toward a DC-SIGN+ (CD209) intermediate cell and impair differentiation into dendritic cellsDaniela Giordano
Department of Immunology, University of Washington, Seattle, WA 98195, USA
J Immunol 171:6421-30. 2003..At the same time, these signals promote development of an active intermediate cell type having properties between those of macrophages and DCs, which might contribute to the innate immune response in the periphery... - The two GAF domains in phosphodiesterase 2A have distinct roles in dimerization and in cGMP bindingSergio E Martinez
Departments of Pharmacology, and Biochemistry and Biological Structure, Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA
Proc Natl Acad Sci U S A 99:13260-5. 2002..Moreover, this cGMP site is located well away from the region predicted by previous mutagenesis and structural genomic approaches... - The high-affinity cAMP-specific phosphodiesterase 8B controls steroidogenesis in the mouse adrenal glandLi Chun Lisa Tsai
University of Washington, Department of Pharmacology, Seattle, WA 98195 7280, USA
Mol Pharmacol 79:639-48. 2011..These findings further suggest PDE8B as a potential therapeutic target for the treatment of several different adrenal diseases... - Cyclic GMP phosphodiesterases and regulation of smooth muscle functionSergei D Rybalkin
Department of Pharmacology, University of Washington, Seattle, Wash 98195, USA
Circ Res 93:280-91. 2003..In humans, this decrease is caused in large part by induction of another Ca2+/calmodulin-dependent PDE (PDE1C) that allows the brake to be released and proliferation to start... - Differential regulation of endothelial cell permeability by cGMP via phosphodiesterases 2 and 3James Surapisitchat
University of Washington, Department of Pharmacology, 1959 NE Pacific St, Seattle, WA 98195 7280, USA
Circ Res 101:811-8. 2007..These findings suggest that the effect of increasing concentrations of cGMP on endothelial permeability is biphasic, which, in large part, is attributable to the relative amounts of PDE2A and PDE3A in endothelial cells... - Hydrolysis products of cAMP analogs cause transformation of Trypanosoma brucei from slender to stumpy-like formsSunil Laxman
Department of Pharmacology, Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA 98195, USA
Proc Natl Acad Sci U S A 103:19194-9. 2006..These data suggest that the slender-to-stumpy transformation of T. brucei may not be mediated directly by cAMP and also raise the possibility of using such adenosine analogs as antitrypanosomal drugs... - PDE1B2 regulates cGMP and a subset of the phenotypic characteristics acquired upon macrophage differentiation from a monocyteAndrew T Bender
Department of Pharmacology, University of Washington Medical School, Seattle, WA 98195 7280, USA
Proc Natl Acad Sci U S A 103:460-5. 2006.... - Solution structure of the cGMP binding GAF domain from phosphodiesterase 5: insights into nucleotide specificity, dimerization, and cGMP-dependent conformational changeClemens C Heikaus
Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA
J Biol Chem 283:22749-59. 2008..The features of the PDE5 regulatory domain revealed here provide an initial structural basis for future investigations of the regulatory mechanism of PDE5 and the design of GAF-specific regulators of PDE5 function... - Differentiation of human monocytes in vitro with granulocyte-macrophage colony-stimulating factor and macrophage colony-stimulating factor produces distinct changes in cGMP phosphodiesterase expressionAndrew T Bender
Department of Pharmacology, University of Washington Medical School, Box 357280, Seattle, WA 98195 7280, USA
Cell Signal 16:365-74. 2004..We found that GM-CSF differentiation triggers a small decrease in soluble guanylyl cyclase (sGC) and a large increase in GC-A, while M-CSF significantly decreases sGC... - The structure of the GAF A domain from phosphodiesterase 6C reveals determinants of cGMP binding, a conserved binding surface, and a large cGMP-dependent conformational changeSergio E Martinez
Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA
J Biol Chem 283:25913-9. 2008..The presented crystal structure will help to define the cGMP-dependent regulation mechanism of the PDE6 holoenzyme and its inhibition through Pgamma binding... - PDE5 is converted to an activated state upon cGMP binding to the GAF A domainSergei D Rybalkin
Department of Pharmacology, University of Washington, Seattle, WA 98195 7280, USA
EMBO J 22:469-78. 2003..The data also suggest that development of agonists and antagonists of PDE5 activity based on binding to this site might be possible... - Elevated cyclic AMP and PDE4 inhibition induce chemokine expression in human monocyte-derived macrophagesAngie L Hertz
Department of Pharmacology, University of Washington Medical School, Seattle, WA 98195, USA
Proc Natl Acad Sci U S A 106:21978-83. 2009..These data suggest that chemokine receptor antagonists administered in conjunction with a PDE4 inhibitor may improve both the efficacy and safety of PDE4-inhibitor therapy for chronic inflammatory disorders... - Individual cerebellar Purkinje cells express different cGMP phosphodiesterases (PDEs): in vivo phosphorylation of cGMP-specific PDE (PDE5) as an indicator of cGMP-dependent protein kinase (PKG) activationMasami Shimizu-Albergine
Department of Pharmacology, University of Washington, Seattle, Washington 98195-7280, USA
J Neurosci 23:6452-9. 2003.... - Molecular determinants of cGMP binding to chicken cone photoreceptor phosphodiesteraseDaming Huang
Department of Pharmacology and Medicinal Chemistry, University of Washington, Seattle, Washington 98195, USA
J Biol Chem 279:48143-51. 2004..Moreover the cGMP binding properties of chicken cone PDE6 holoenzyme were very similar to those of the bacterially expressed individual GAF-A or GAF-A/B domains... - Cyclic nucleotide analogs as probes of signaling pathwaysHeiko Poppe
Nat Methods 5:277-8. 2008 - Characterization of a novel cAMP-binding, cAMP-specific cyclic nucleotide phosphodiesterase (TcrPDEB1) from Trypanosoma cruziRocío Díaz-Benjumea
Instituto de Biologia Experimental, Universidad Central de Venezuela, Box 47069, Caracas, Venezuela
Biochem J 399:305-14. 2006.... - Cyclic nucleotide specific phosphodiesterases of the kinetoplastida: a unified nomenclatureStefan Kunz
Institute of Cell Biology, University of Bern, Baltzerstrasse 4, CH-3012 Bern, Switzerland
Mol Biochem Parasitol 145:133-5. 2006 - The cyanobacterial tandem GAF domains from the cyaB2 adenylyl cyclase signal via both cAMP-binding sitesSandra Bruder
Pharmazeutisches Institut, Universitat Tubingen, Morgenstelle 8, D 72076 Tubingen, Germany
Proc Natl Acad Sci U S A 102:3088-92. 2005..The cyaB2 GAF ensemble appears to be an evolutionary intermediate where both GAF domains still participate in allosteric activation by cAMP... - A-kinase anchoring proteins interact with phosphodiesterases in T lymphocyte cell linesAngela L Asirvatham
Veterans Affairs Medical Center, Oregon Health and Sciences University, Portland 97239, USA
J Immunol 173:4806-14. 2004..In summary, these data suggest that AKAPs interact with both PKA and PDE in T lymphocytes and thus are a key component of the signaling complex regulating T cell activation... - mRNA expression patterns of the cGMP-hydrolyzing phosphodiesterases types 2, 5, and 9 during development of the rat brainWilma C G van Staveren
Department of Psychiatry and Neuropsychology, Division Cellular Neuroscience, Maastricht University, European Graduate School of Neuroscience EURON, 6200 MD Maastricht, The Netherlands
J Comp Neurol 467:566-80. 2003..Thus, it appears that differential expression of PDE isoforms may provide a mechanism to match cGMP hydrolysis to the functional demands of individual brain regions... - Cloning and characterization of a cAMP-specific phosphodiesterase (TbPDE2B) from Trypanosoma bruceiAna Rascon
Instituto de Biologia Experimental, Universidad Central de Venezuela, Apartado 47 069, Caracas 1041 A, Venezuela
Proc Natl Acad Sci U S A 99:4714-9. 2002..Therefore, parasite PDEs, including this one, have the potential to be attractive targets for selective drug design...
Research Grants
- Regulation of Cellular Functions by Cyclic Nucleotide Phosphodiesterase 8Joseph A Beavo; Fiscal Year: 2010....
- PHOTORECEPTOR PHOSPHODIESTERASE STRUCTURE/FUNCTIONJoseph Beavo; Fiscal Year: 2001..Finally, we want to test the idea that the PDE6 delta subunit will also interact with several other enzymes in the visual transduction cascade and that their functions too may be regulated by similar mechanisms. ..
- PHOTORECEPTOR PHOSPHODIESTERASE STRUCTURE & FUNCTIONJoseph Beavo; Fiscal Year: 1993..These approaches should complement each other and allow the structural basis for functional properties to be studied...
- PDE1C REGULATION OF VASCULAR SMOOTH MUSCLE PROLIFERATIONJoseph Beavo; Fiscal Year: 2001..Change in SMC phenotype to the proliferative state in cells overexpressing PDE1C will be determined. Inhibitors of PDE1C should conversely, prevent SMC proliferation. ..
- Regulation of Cellular Functions by Cyclic Nucleotide Phosphodiesterase 8Joseph Beavo; Fiscal Year: 2009..Since most heart attacks have an arrhythmia component the relevance to public health is obvious. ..
- METABOLISM AND FUNCTION OF CYCLIC NUCLEOTIDESJoseph Beavo; Fiscal Year: 2007..The methods make use of specific antisense and siRNA expression under the graded control of drug inducible promoters. ..
- METABOLISM AND FUNCTION OF CYCLIC NUCLEOTIDEJoseph Beavo; Fiscal Year: 2003..Similar approaches with other cytokines will also be carried out. These studies have the potential to define a whole new molecular mechanism of action for cytokines and a whole new general physiological role for PDE3B. ..
- METABOLISM AND FUNCTION OF CYCLIC NUCLEOTIDESJoseph Beavo; Fiscal Year: 1993..Finally, two promising new techniques for isolation of cDNAs for novel cyclic nucleotide phosphodiesterases will be explored...
- METABOLISM AND FUNCTION OF CYCLIC NUCLEOTIDESJoseph Beavo; Fiscal Year: 1990..Finally, questions about the molecular relatedness of each of the isozymes will be addressed by determining primary sequence for several of the isozymes...