Joseph Beavo

Summary

Affiliation: University of Washington
Country: USA

Publications

  1. pmc cAMP-specific phosphodiesterases 8A and 8B, essential regulators of Leydig cell steroidogenesis
    Masami Shimizu-Albergine
    Department of Pharmacology, University of Washington, Seattle, Washington 98195 7280, USA
    Mol Pharmacol 81:556-66. 2012
  2. ncbi request reprint Cyclic nucleotide research -- still expanding after half a century
    Joseph A Beavo
    Department of Pharmacology, University of Washington, Seattle, Washington 98195 7280, USA
    Nat Rev Mol Cell Biol 3:710-8. 2002
  3. pmc Crystal structure of the tandem GAF domains from a cyanobacterial adenylyl cyclase: modes of ligand binding and dimerization
    Sergio E Martinez
    Department of Pharmacology, University of Washington, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 102:3082-7. 2005
  4. ncbi request reprint Trypanosome cyclic nucleotide phosphodiesterase 2B binds cAMP through its GAF-A domain
    Sunil Laxman
    Department of Pharmacology, University of Washington, Seattle, Washington 98195 7280, USA
    J Biol Chem 280:3771-9. 2005
  5. pdf Cyclic nucleotide signaling mechanisms in trypanosomes: possible targets for therapeutic agents
    Sunil Laxman
    Department of Pharmacology, University of Washington School of Medicine, Seattle, WA 98105, USA
    Mol Interv 7:203-15. 2007
  6. ncbi request reprint Molecular determinants for cyclic nucleotide binding to the regulatory domains of phosphodiesterase 2A
    Albert Y Wu
    Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA
    J Biol Chem 279:37928-38. 2004
  7. ncbi request reprint Cyclic nucleotides promote monocyte differentiation toward a DC-SIGN+ (CD209) intermediate cell and impair differentiation into dendritic cells
    Daniela Giordano
    Department of Immunology, University of Washington, Seattle, WA 98195, USA
    J Immunol 171:6421-30. 2003
  8. pmc The two GAF domains in phosphodiesterase 2A have distinct roles in dimerization and in cGMP binding
    Sergio 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
  9. pmc The high-affinity cAMP-specific phosphodiesterase 8B controls steroidogenesis in the mouse adrenal gland
    Li Chun Lisa Tsai
    University of Washington, Department of Pharmacology, Seattle, WA 98195 7280, USA
    Mol Pharmacol 79:639-48. 2011
  10. ncbi request reprint Cyclic GMP phosphodiesterases and regulation of smooth muscle function
    Sergei D Rybalkin
    Department of Pharmacology, University of Washington, Seattle, Wash 98195, USA
    Circ Res 93:280-91. 2003

Collaborators

  • Daniela Giordano
  • Laurence L Brunton
  • Kenji Omori
  • MICHAEL GOY
  • Jan de Vente
  • Johannes L Bos
  • Holger Rehmann
  • Sunil Laxman
  • Robert Feil
  • Sergio E Martinez
  • Masami Shimizu-Albergine
  • Sergei D Rybalkin
  • Andrew T Bender
  • Li Chun Lisa Tsai
  • Xiao bo Tang
  • Ana Rascon
  • Clemens C Heikaus
  • Thomas R Hinds
  • Sandra Bruder
  • Albert Y Wu
  • Angie L Hertz
  • Rachel E Klevit
  • Heiko Poppe
  • James Surapisitchat
  • Stefan Kunz
  • Rocío Díaz-Benjumea
  • Jürgen U Linder
  • Chen Yan
  • Joachim E Schultz
  • Ning Zheng
  • Daming Huang
  • Angela L Asirvatham
  • Wilma C G van Staveren
  • Irina G Rybalkina
  • Enrico Patrucco
  • Kimberly C Smith
  • Mark Gilchrist
  • Paul S Amieux
  • Alan Aderem
  • Stein O Doskeland
  • Catherine M Eakin
  • Frank Schwede
  • Peter S Brzovic
  • Ponni Rajagopal
  • Hans Gottfried Genieser
  • Monica R Sekharan
  • Joseph R Stout
  • Elke Butt
  • Anne E Christensen
  • Kye Im Jeon
  • Maximiliano A D'Angelo
  • Yasmin Shakur
  • Laurent Wentzinger
  • Michael Oberholzer
  • Mirtha M Flawia
  • Andrea Johner
  • Roya Zoraghi
  • Thomas Seebeck
  • Sharron H Francis
  • Anita Schultz
  • Catalin Doneanu
  • Daniel W Carr
  • Kaori Ikeda
  • Sarah G Galligan
  • Cari L Ostenson
  • Michael P Davey
  • Robynn V Schillace
  • Valeria Vasta
  • Franz Hofmann
  • Wiebke Wolfsgruber
  • Harry W M Steinbusch
  • David R Repaske
  • Karin E Bornfeldt
  • Marjanne Markerink-van Ittersum
  • Jun Kotera
  • Natalie A Glavas
  • Jonathan B Schaefer
  • Stewart Turley
  • Wim G J Hol
  • Scott H Soderling

Detail Information

Publications27

  1. pmc cAMP-specific phosphodiesterases 8A and 8B, essential regulators of Leydig cell steroidogenesis
    Masami 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...
  2. ncbi request reprint Cyclic nucleotide research -- still expanding after half a century
    Joseph 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...
  3. pmc Crystal structure of the tandem GAF domains from a cyanobacterial adenylyl cyclase: modes of ligand binding and dimerization
    Sergio 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...
  4. ncbi request reprint Trypanosome cyclic nucleotide phosphodiesterase 2B binds cAMP through its GAF-A domain
    Sunil 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...
  5. pdf Cyclic nucleotide signaling mechanisms in trypanosomes: possible targets for therapeutic agents
    Sunil 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...
  6. ncbi request reprint Molecular determinants for cyclic nucleotide binding to the regulatory domains of phosphodiesterase 2A
    Albert 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...
  7. ncbi request reprint Cyclic nucleotides promote monocyte differentiation toward a DC-SIGN+ (CD209) intermediate cell and impair differentiation into dendritic cells
    Daniela 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...
  8. pmc The two GAF domains in phosphodiesterase 2A have distinct roles in dimerization and in cGMP binding
    Sergio 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...
  9. pmc The high-affinity cAMP-specific phosphodiesterase 8B controls steroidogenesis in the mouse adrenal gland
    Li 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...
  10. ncbi request reprint Cyclic GMP phosphodiesterases and regulation of smooth muscle function
    Sergei 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...
  11. ncbi request reprint Differential regulation of endothelial cell permeability by cGMP via phosphodiesterases 2 and 3
    James 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...
  12. pmc Hydrolysis products of cAMP analogs cause transformation of Trypanosoma brucei from slender to stumpy-like forms
    Sunil 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...
  13. pmc PDE1B2 regulates cGMP and a subset of the phenotypic characteristics acquired upon macrophage differentiation from a monocyte
    Andrew 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
    ....
  14. pmc Solution structure of the cGMP binding GAF domain from phosphodiesterase 5: insights into nucleotide specificity, dimerization, and cGMP-dependent conformational change
    Clemens 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...
  15. ncbi request reprint Differentiation of human monocytes in vitro with granulocyte-macrophage colony-stimulating factor and macrophage colony-stimulating factor produces distinct changes in cGMP phosphodiesterase expression
    Andrew 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...
  16. pmc 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 change
    Sergio 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...
  17. pmc PDE5 is converted to an activated state upon cGMP binding to the GAF A domain
    Sergei 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...
  18. pmc Elevated cyclic AMP and PDE4 inhibition induce chemokine expression in human monocyte-derived macrophages
    Angie 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...
  19. ncbi request reprint 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) activation
    Masami Shimizu-Albergine
    Department of Pharmacology, University of Washington, Seattle, Washington 98195 7280, USA
    J Neurosci 23:6452-9. 2003
    ....
  20. ncbi request reprint Molecular determinants of cGMP binding to chicken cone photoreceptor phosphodiesterase
    Daming 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...
  21. doi request reprint Cyclic nucleotide analogs as probes of signaling pathways
    Heiko Poppe
    Nat Methods 5:277-8. 2008
  22. pmc Characterization of a novel cAMP-binding, cAMP-specific cyclic nucleotide phosphodiesterase (TcrPDEB1) from Trypanosoma cruzi
    Rocío Díaz-Benjumea
    Instituto de Biologia Experimental, Universidad Central de Venezuela, Box 47069, Caracas, Venezuela
    Biochem J 399:305-14. 2006
    ....
  23. ncbi request reprint Cyclic nucleotide specific phosphodiesterases of the kinetoplastida: a unified nomenclature
    Stefan Kunz
    Institute of Cell Biology, University of Bern, Baltzerstrasse 4, CH 3012 Bern, Switzerland
    Mol Biochem Parasitol 145:133-5. 2006
  24. pmc The cyanobacterial tandem GAF domains from the cyaB2 adenylyl cyclase signal via both cAMP-binding sites
    Sandra 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...
  25. ncbi request reprint A-kinase anchoring proteins interact with phosphodiesterases in T lymphocyte cell lines
    Angela 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...
  26. ncbi request reprint mRNA expression patterns of the cGMP-hydrolyzing phosphodiesterases types 2, 5, and 9 during development of the rat brain
    Wilma 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...
  27. pmc Cloning and characterization of a cAMP-specific phosphodiesterase (TbPDE2B) from Trypanosoma brucei
    Ana 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 Grants47

  1. Regulation of Cellular Functions by Cyclic Nucleotide Phosphodiesterase 8
    Joseph A Beavo; Fiscal Year: 2010
    ....
  2. PHOTORECEPTOR PHOSPHODIESTERASE STRUCTURE/FUNCTION
    Joseph 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. ..
  3. PHOTORECEPTOR PHOSPHODIESTERASE STRUCTURE & FUNCTION
    Joseph Beavo; Fiscal Year: 1993
    ..These approaches should complement each other and allow the structural basis for functional properties to be studied...
  4. PDE1C REGULATION OF VASCULAR SMOOTH MUSCLE PROLIFERATION
    Joseph 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. ..
  5. Regulation of Cellular Functions by Cyclic Nucleotide Phosphodiesterase 8
    Joseph Beavo; Fiscal Year: 2009
    ..Since most heart attacks have an arrhythmia component the relevance to public health is obvious. ..
  6. METABOLISM AND FUNCTION OF CYCLIC NUCLEOTIDES
    Joseph Beavo; Fiscal Year: 2007
    ..The methods make use of specific antisense and siRNA expression under the graded control of drug inducible promoters. ..
  7. METABOLISM AND FUNCTION OF CYCLIC NUCLEOTIDE
    Joseph 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. ..
  8. METABOLISM AND FUNCTION OF CYCLIC NUCLEOTIDES
    Joseph Beavo; Fiscal Year: 1993
    ..Finally, two promising new techniques for isolation of cDNAs for novel cyclic nucleotide phosphodiesterases will be explored...
  9. METABOLISM AND FUNCTION OF CYCLIC NUCLEOTIDES
    Joseph 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...