NAME:      JOSEPH ANDERS BEAVO, JR.

 

WORK ADDRESS:                                                 HOME ADDRESS:

            Dept. of Pharmacology                                   2309 NW 86th St Street

            Box 357280                                                   Seattle, WA  98l17

            University of Washington                             

            Seattle, WA  98l95-7280                                

            Phone (206) 543-4006 (wk)                            206-789-8001 (hm), 206-853-8140 (cell)

            FAX   (206) 685-3822                                    email <beavo@u.washington.edu>

 
EDUCATION:

            Stetson University, Deland, FL , B.S. (Chemistry-Biology)

            Vanderbilt University, Nashville, TN, Ph.D. (Physiology)

                        Major Professors: Drs. E. W. Sutherland & J. G. Hardman

            University of California, Davis, CA, Postdoctoral Training

                        Department of Biological Chemistry, Director:  Dr. Edwin G. Krebs

 
ACADEMIC APPOINTMENTS:

1986-present   Professor, Department of Pharmacology

                        University of Washington

 
l977-1986        Asst. & Assoc. Professor, Department of Pharmacology

                        University of Washington

 
l974-l977         Adjunct Assistant Professor, Dept. of Biological Chemistry

                        University of California, Davis

 
NATIONAL MEMBERSHIPS, RESPONSIBILITIES & AWARDS:

1976-1981       Established Investigator, American Heart Assoc.

1980-               American Society of Pharm. & Exp. Therapeutics (ASPET)

1979-1998       NIH, Physiological Chemistry, Biochemistry, Endocrinology, and

                         Pharmacology Ad Hoc Study Section Member

1984-1986       American Heart Association Study Section Member

1984-1987       Editorial Board, Molec. & Cell. Endocrinology

1986-1990       Associate Editor, Molecular Pharmacology

1989-1994       Editorial Board, J. Biol. Chem.

1995-2000       Editorial Board, Pharmacological Reviews

1993-1999       Program Committee, ASPET

1996-present   Member National Academy of Sciences,

1999-2005       Editorial Board PNAS

2000- 2009      Councilor, ASPET

2008- 2009      President, ASPET

STUDENTS TRAINED

PAST TRAINEES:  PREDOCTORAL:                     CURRENT POSITION

Dr. Stuart Builder                    '76-78  Ph.D.                Sr. Scientist, Genentech, Inc.

Dr. R. Scott Hansen                '77-84  Ph.D.                Res Assoc. Prof. Dept. of Medical

                                                                                   Genetics, U. of Washington

Dr. Timothy Martins               '79-84  Ph.D.                Staff Scientist, ICOS Inc.

                                                                                   Bothell, WA

Dr. Scott Harrison                   '81-86  Ph.D.               Staff Scientist at Genetic Systems

                                                                                      Andover, MA

Dr. Peter Gillespie                   '83-88  Ph.D.               Prof., Dept Neurosci. Oregon HSU

Dr. Jeffrey Novak                   '84-90  Ph.D.               Prof, J. Bastier College

Dr. Ron MacFarland               '84-90  Ph.D.               Director Toxicology, AnorMed, Inc.

Dr. Jeri Beltman                      '86-93  Ph.D.               Staff Scientist, ONYX

Dr. Timothy Bloom                 '88-96  Ph.D.               Assoc. Prof, Campbell University

Dr. Chen Yan                          '92-96  Ph.D.               Assoc. Prof, Univ of Rochester

Dr. Stephanie Florio                '88-96  Ph.D.               Research Scientist, Amgen Inc.

Dr. Dawn Julifs                       '88-97  Ph.D.               Staff Scientist, Pfizer.

Dr. Scott Soderling                 '94-99  Ph.D.               Asst. Prof., Duke Univ.

Dr. Linsong Li                        '96-99  Ph.D.               Professor, Bejing University

Dr. Terry Cook                     '95-01  Ph.D.               Research Pharma Services, Medical Writer

Dr. Albert Wu                       ’98-03  Ph.D.              Resident Opthamology, U. Utah

Dr. Daming Huang                 ’98-04  Ph.D.              Private Business

Dr. Sunil Laxman                    '02-06  Ph.D               Postdoctoral Fellow U. Texas SW

Dr. James Surapisitchat           ’01-08  PhD               Postdoctoral Fellow, U. of Toronto

 

PAST TRAINEES: POSTDOCTORAL:                    CURRENT POSITION

 Marc C. Mumby, Ph.D.          '79-83                          Prof. of Pharmacology

                                                                                       Univ. of Texas, Dallas

Richard Hurwitz, M.D.            '80-84                          Assoc. Prof. Medicine

                                                                                       Baylor University

Norbert Beier, Ph.D.               '84-86                          Group Leader, Merck Inc.

                                                                                       Darmstadt, FDG

Colin Macphee, Ph.D.             '83-86                          Senior Scientist

                                                                                       Smith/Kline/Glaxo

David Reifsnyder, Ph.D.         '83-88                         Assoc Dir Recovery Process,

                                                                                       Chiron, Inc. San Francisco

Harry Charbonneau, Ph.D.      '85-92                          Assoc. Prof. of Biochemistry,

                                                                                       Purdue Univ.

Stephen Stroop, Ph.D.             '86-89                          Director Protein Biochemistry,

                                                                                       ID Medical, Bothell, WA

Vince Florio, Ph.D.                 '90-92                          Staff Scientist, ICOS, Inc

                                                                                       Bothell, WA

Rabi Prusti, Ph.D.                   '88-92                          Director Quality Control, 

                                                                                       CancerVax,  Inc

J. Kelley Bentley, Ph.D.          '90-94                         Res Assoc. Prof., Univ. of Michigan

                                                                                       Ann Arbor, MI

Josep V. Planas, Ph.D.            '95-96                         Assoc.  Prof. Univ. de Barcelona,

                                                                                       Barcelona, Spain

Fiona Burns,  Ph.D.                '94-96                          Res. Scientist, Biosource Intl.

Wm. Sonnenburg, Ph.D.         '87-99                          Staff Scientist, Lexicon Genetics Inc

                                                                                        The Woodlands , Tx

Alan Zhao, Ph.D.                     '94-99                          Assoc. Prof., U. of Pittsburg

Joanna Hetman, M.D.             ‘98-00                                     MD, Louisville, KY

Natalie Glavas,  Ph.D.             '97-02                          Staff Scientist, Inimex Pharmaceuticals Inc                                                                                              Vancouver, BC

Daniella Giordano, Ph.D.        '99-03                          Senior Fellow, Immunology, UW

Jennifer Glick, Ph.D.               ‘98-04                         Maternity Leave (permanent)

Anita Narula, Ph.D.                 ’03-04                         Maternity Leave (permanent)

Sergio Martinez, Ph.D.            ‘95-07                         Res Assoc, Rutgers Univ

Valeria Vasta, Ph.D.                ‘99-07                         Scientist Children’s Hosp Res. Inst.

Andrew Bender, Ph.D.            ‘01-07                         Scientist, Eisai Inc., Andover, MA

 
(Sabbatical Trainees)

Jerry Reek, Ph.D.                    '84                               Professor, Kansas State U.

Bulent Mutus, Ph.D.              '89                               Professor, U. of Windsor

Rick Cote. Ph.D.                     '96                               Professor, U. of New Hampshire

Ana Rascon, Ph.D.                  '99                               Assoc. Professor, U. of Caracas

 

CURRENT TRAINEES         PREDOCTORAL       FUNDING SOURCE

 Lisa Tsai                                  ’04                              NIH Training Grant

Steve Kraynik                          ’06                              NIH Training Grant

Angie Hertz                             ’06                              NIH Training Grant

Candace Adamo                      ’07                              Research Grant

Claude Beltejar                        ’10                              Research Grant

CURRENT Members                         POSTDOCTORAL    FUNDING SOURCE

Sergei Rybalkin, Ph.D.                         ’92 -                            Am. Lung Assoc. Research Grant

Masami Shimizu-Albergine                   ’04 -                            NIH Research Grant

Enrico Patrucco, Ph.D.                        ’05 -                             LeDucque Foundation Grant

Xiaoling Zhang, Ph.D.                          ’09 -                            NIH Research Grant

 

BIBLIOGRAPHY

 

Thesis:  Cyclic GMP and Cyclic AMP Hydrolysis by Beef and Rat Tissues

1.     Beavo, J. A., Hardman, J. G., and Sutherland, E. W. (l970) Hydrolysis of Cyclic Guanosine and Adenosine-3',5'-Monophosphates by Rat and Bovine Tisssues.  J. Biol. Chem. 245:5649-5655.

2.     Beavo, J. A., Rogers, N. L., Crofford, O. B., Hardman, J. G., Sutherland, E. W. and Newman, E. V. (l970) Effects of Xanthine Derivatives on Lipolysis and on Adenosine-3',5'-Monophosphate Phosphodiesterase Activity.  Mol. Pharmacol. 6:597-603.

3.     Beavo, J. A., Rogers, N.L., Crofford, O. B., Baird, C. E., Hardman, J. G., Sutherland, E. W. and Newman, E. V. (l97l) Effects of Phosphodiesterase Inhibitors on Cyclic AMP Levels and on Lipolysis.  Ann. N.Y. Acad. Sci. 185:l29-l36.

4.     Beavo, J. A., Hardman, J. G. and Sutherland, E. W. (l97l) Stimulation of Adenosine-3',5'-Monophosphate Hydrolysis by Guanosine 3',5'-Monophosphate.  J. Biol. Chem. 246:384l-3846.

5.     Hardman, J. G., Beavo, J. A., Gray, J. P., Chrisman, T. D., Patterson,W. D. and Sutherland, E. W. (l97l) Formation and Metabolism of Cyclic GMP. Ann. N.Y. Acad. Sci. 185:27.

6.     Krebs, E. G., Beavo, J. A., Brostrom, C. O., Corbin, J. D., Hayakawa, T. and Walsh, D. A.  (l97l) Mechanism of Action of Cyclic AMP in the Activation of Phosphorylase Kinase.  In: International Symposium on Metabolic Interconversion of Enzymes, Rottach-Egern, West Germany, October,  Springer-Verlag, Berlin, Heidelberg and New York, pp. ll3-ll7.

7.     Beavo, J. A., Bechtel, P. G. and Krebs, E. G. (l975) Preparation of Homogeneous c AMP-Dependent Protein Kinase and its Subunits from Rabbit Skeletal Muscle.  In: Methods in Enzymology, 38C, Academic Press, New York, pp.  299-308.

8.     Krebs, E. G., Beavo, J. A., Bechtel, P. J., England, P. J., Huang, T. S. and Stull, J. T. (l974) Cyclic AMP and Protein Phosphorylation Reactions in Muscle. In: Exploratory Concepts in Muscle, Excerpta Medica, Amsterdam, pp. 43l-448.

9.     Beavo, J. A., Bechtel, P. J. and Krebs, E. G. (l974) Activation of Protein Kinase by Physiological Concentration of Cyclic AMP.  Proc. Nat. Acad. Sci. 71:3580-3583.

10.      Dills, W. L., Beavo, J. A., Bechtel, P. J. and Krebs, E. G. (l975) Purification of Rabbit Skeletal Muscle Protein Kinase Regulatory Subunit Using Cyclic Adenosine-3,5'-Monophosphate Affinity Chromatography.  Biochem. Biophys. Res. Comm. 62:70-77.

11.      Beavo, J. A., Bechtel, P. J., Krebs, E. G. (l975) Mechanisms of Control cAMP Dependent Protein Kinase from Skeletal Muscle.  Advances in Cyclic Nucleotide Research 5:24l-25l.

12.      Shizuta, Y., Beavo, J. A., Bechtel, P. J., Hofmann, F. and Krebs, E. G. (l975) Reversibility of Adenosine 3',5'-Monophosphate-Dependent Protein Kinase Reactions.  J. Biol. Chem. 250:689l-6896.

13.      Hofmann, F., Beavo, J. A., Bechtel, P. J. and Krebs, E. G. (l975) Comparison of Adenosine-3',5'-Monophosphate-Dependent Protein Kinases from Rabbit Skeletal and Bovine Heart Muscle.  J. Biol. Chem. 250:7795-780l.

14.      Dills, W. L., Beavo, J. A., Bechtel, P. J., Myers, K. R., Sakai, L. J. and Krebs, E. G. (l976) Binding of Adenosine 3',5'-Monophosphate-Dependent Protein Kinase Regulatory Subunit to Immobilized Cyclic Nucleotide Derivatives.  Biochemistry 15:3724-373l.

15.      Bechtel, P. J., Beavo, J. A. and Krebs, E. G. (l977) Purification and Characterization of the Catalytic Subunit of Skeletal Muscle Adenosine 3',5'-Monophosphate-Dependent Protein Kinase.  J. Biol. Chem. 252:2691-2697.

16.      Steiner, A. L., Koide, Y., Earp, H. S., Bechtel, P. J. and Beavo, J. A. (l978) Compartmentalization of Cyclic Nucleotides and Cyclic AMP-Dependent Protein Kinases in Rat Liver:  Immunocytochemical Demonstration.  Adv. in Cylic Nuc. Res. 9:69l-705.

17.      Steiner, A. L., Koide, Y., Spruill, W. A. and Beavo, J. A. (l978) The Distribution of Cyclic Nucleotides and Their Protein Kinases in Tissues:  An Immunocytochemical Approach.  Adv. Pharm. and Exp. Ther. 3:207-2l9.

18.      Dills, W. L., Goodwin, C. O., Lincoln, T. M., Beavo, J. A. Bechtel, P. J., Corbin, J. D. and Krebs, E. G. (l978) Purification of Cyclic Nucleotide Receptors by Cyclic Nucleotide Affinity Chromatography.  Adv. Cyclic Nucleotide Res. 10:199-218.

19.      Krebs, E. G. and Beavo, J. A. (l979) Phosphorylation-Dephosphorylation of Enzymes.  Ann. Rev. Biochem. 48:923-959.

20.      Kapoor, C. L., Beavo, J. A. and Steiner, A. L. (l979) Radioimmunoassay of the Regulatory Subunit of Type I cAMP-dependent protein kinase.  J. Biol. Chem. 254:l2427-32.

21.      Builder, S. E., Beavo, J.A. and Krebs, E. G. (l980) Stoichiometry of cAMP and l,N6-Etheno-cAMP Binding to Protein Kinase.  J. Biol. Chem. 255:2350-54.

22.      Builder, S. E., Beavo, J. A. and Krebs, E. G. (l980) The Mechanism of Activation of Bovine Skeletal Muscle Protein Kinase by Adenosine 3',5'-Monophosphate.  J. Biol. Chem. 255:35l4-l9 .

23.      Mumby, M. and Beavo, J. A. (l980) Production and Characterization of Monoclonal Antibodies to Type II Regulatory Subunit of Cyclic AMP-Dependent Protein Kinase.  Proc. W. Pharmacol. Soc. 23:369-73.

24.      Browne, C. L., Lockwood, A. H., Su, J., Beavo, J. A., and Steiner, A. L. (1980) Immunofluorescent Localization of Cyclic Nucleotide-dependent Protein Kinases on the Mitotic Apparatus of Cultured Cells.  J. Cell Biol. 87:336-45.

25.      Beavo, J. A., and Hansen, R. S. (1981) Enzyme Purification Utilizing Conformation Specific Monoclonal Antibodies in Monoclonal Antibodies in Endocrine Research, Fellows and Ersenbarth, Eds. Raven Press N.Y., 157-166.

26.      Beavo, J. A. and Mumby, M. C. (1981) cAMP Dependent phosphorylation. Handbook of Pharmacology. Chapter 11, Springer-Verlag, Heidelberg, 363-389.

27.      Doherty, P., Tsao, J., Schimmer, B. P., Mumby, M. and Beavo, J. A. (1981) cAMP-dependent protein kinase and regulation of adreno-cortical functions - a genetic evaluation.  Cold Spring Harbor Symposium -Protein Phosphorylation.  8:211-226.

28.      Builder, S. E., Beavo, J. A. and Krebs, E. G. (1981) The Mechanismn of Activation and Inactivation of cAMP Dependent Protein Kinase: Several Lines of Evidence.  Cold Spring Harbor Symposium - Protein Phosphorylation.  8:33-44.

29.      Mumby, M. and Beavo, J. A. (1981) Unique Properties of Monoclonal Antibodies as Probes of the Structure, Function, and Regulations of Protein Kinases.  Cold Spring Harbor Symposium - Protein Phosphorylation. 8:105-124.

30.      Kapoor, C. L., Beavo, J. A. and Steiner, A. L. (1981) Radioimmunoassay of the Regulatory Subunit of Type I cAMP-Dependent Protein Kinase.  Methods in Enzymology- Immunochemical Techniques.  H.V. Vunakis and J.J.LaGone, Ed. Academic Press, NY, NY.

31.      Cumming, R., Koide, Y., Krigman, M. R., Beavo, J. A., and Steiner, A. L. (1981) Immunofluorescent localization of regulatory and catalytic subunits of cAMP- dependent protein Kinase in neuronal and glial cell types of the central nervous system.  Neuroscience 6:953-61.

32.      Spruill, W. A., Koide, Y., Huang, H. L., Levine, S. N., Ong, S. H., Steiner, A. L., and Beavo, J. A. (1981) Immunocytochemical Localization of Cyclic Guanosine Monophosphate-dependent Protein Kinase in Endocrine Tissues.  Endocrinology 109:2239-48.

33.      Koide, Y., Beavo, J. A., Kapoor, C. L., Spruill, W. A., Huang, H. L., Levine, S. N., Ong, S. L., Bechtel, P. J., Yount, W. J., and Steiner, A. L. (1981) Hormonal Effects on the Immunocytochemical Location of 3'5' Cyclic Adenosine Monophosphate-dependent Protein Kinase in Rat Tissues.  Endocrinology 109:2226-38.

34.      Martins, T. J., Mumby, M. C., and Beavo, J. A. (1982) Purification and Characterization of a Cyclic GMP Stimulated Cyclic Nucleotide Phosphodiesterase from Bovine Tissues. J. Biol. Chem. 257:1973-1979.

35.      Hansen, R. S. and Beavo, J. A. (1982) Purification of Two Calcium/calmodulin dependent Forms of Cyclic Nucleotide Phosphodiesterase Using Conformation-Specific Monoclonal Antibody Chromatography. PNAS 79:2788-92.

36.      Doherty, P. J., Tsao, J., Schimmer, B. P., Mumby, M. C., and Beavo, J. A. (1982) Alteration of the Regulatory Subunit of Type 1 cAMP-dependent Protein Kinase in Mutant Y-1 Adrenal Cells Resistant to 8-Bromoadenosine 3':5'-Monophosphate.  J. Biol. Chem. 257:5877-83.

37.      Beavo, J. A., Hansen, R. S., Harrison, S. A., Hurwitz, R. L., Martins, T. J. and Mumby, M. C. (1982) Identification and Properties of Cyclic Nucleotide Phosphodiesterases.  Mol. Cell Endocrinol. 28:387-410.

38.      Mumby, M. C., Martins, T. J., Chang, M. L., and Beavo, J. A. (1982) Identification of cGMP-stimulated Cyclic Nucleotide Phosphodiesterase in Lung Tissue with Monoclonal Antibodies.  J. Biol. Chem. 257:13283-13290.

39.      Weldon, S. L., Mumby, M. C., Beavo, J. A., and Taylor, S. S. (1983) Monoclonal Antibodies as Structural Probes of Surface Residues in the Regulatory Subunit of cAMP-dependent Protein Kinase II from Porcine Heart.  J. Biol. Chem. 258:1129-1135.

40.      Hurwitz, R. L., Hansen, R. S., Harrison, S. A., Martins, T. J., Mumby, M. C., and Beavo, J. A. (1984) Immunologic Approaches to the Study of Cyclic Nucleotide Phosphodiesterases.  Adv. Cyc. Nuc. Res. 16:89-106.

41.      Hurwitz, R. L., Bunt-Milam, A. H., and Beavo, J. A. (1984) Immunologic Characterization of the Photoreceptor Outer Segment Cyclic GMP Phosphodiesterase.  J. Biol. Chem. 259:8612-8618.

42.      Hurwitz, R. L., and Beavo, J. A. (1984) Immunotitration analysis of the Rod Outer Segment Phosphodiesterase.  Adv. Cyc. Nuc. Res. 17:239-248.

43.      Hurwitz, R. L., Bunt-Milam, A. H., Chang, M. L., and Beavo, J. A. (1985) cGMP Phosphodiesterase in Rod and Cone Outer Segments of the Retina.  J. Biol. Chem. 260:568-573.

44.      Harrison, S. A., Chang, M. L., and Beavo, J. A. (1986) Differential Inhibition of Cardiac Cyclic Nucleotide Phosphodiesterase Isozymes by Cardiotonic Drugs.  Circulation 73:(suppl III) 109-116.

45.      Harrison, S. A., Reifsnyder, D. H., Gallis, B., Cadd, G. G., and Beavo, J. A. (1986) Isolation and Characterization of Bovine Cardiac Muscle cGMP-Inhibited Phosphodiesterase: A Receptor for New Cardiotonic Drugs.  Mol. Phcol. 29:506-514.

46.      Hansen, R. S. and Beavo, J. A. (1986) Differential Recognition of Calmodulin/Enzyme Complexes by a Conformation-Specific Anti-calmodulin Monoclonal Antibody.  J. Biol. Chem. 261:14636-14645.

47.      Macphee, C. H., Harrison, S. H., and Beavo, J. A. (1986) Immunological Identification of the Major Platelet Low Km cAMP Phosphodiesterase: A Probable Target for Anti-Thrombotic Agents.  Proc. Nat. Acad. Sci. USA 83:6660-6663.

48.      Charbonneau, H., Beier, N., Walsh, K. A., and Beavo, J. A. (1986) Identification of a Conserved Domain among Cyclic Nucleotide Phosphodiesterases from Diverse Species.  Proc. Nat. Acad. Sci. USA 83:9308-9312.

49.      Charbonneau, H., Novack, J. P., MacFarland, R. T., Walsh, K. A., and Beavo, J. A. (1987) Structure and function of calmodulin-dependent phosphodiesterase isozymes  Calcium Binding Proteins and Health and Disease.  Academic Press p505-517.

50.      Harrison, S. A., Beier, N., Martins, T. J. and Beavo, J. A. (1988) Isolation and Comparison of Bovine Heart cGMP-Inhibited and cGMP-Stimulated Phosphodiesterases.  Methods in Enzymology 159:685-701.

51.      Hansen, R. S., Charbonneau, H. and Beavo, J. A. (1988) Purification of Calmodulin-Stimulated Cyclic Nucleotide Phosphodiesterase by Monoclonal Antibody Affinity Chromatography.  Methods in Enzymology 159:543-556.

52.      Macphee, C. H., Reifsnyder, D. H., Moore, T. A., and Beavo, J. A.  Intact cell and cell-free phosphorylation and concomitant activation of a low Km , cAMP phosphodiesterase found in human platelets.  J. Cyc. Nuc. and Prot. Phos. Res.  11:487-496 (1988).

53.      Macphee, C. H., Reifsnyder, D. H., Moore, T. A., Lerea, K. M., and Beavo, J. A. (1988) Phosphorylation results in activation of a cAMP phosphodiesterase in human platelets.  J. Biol. Chem. 263:10353-10358.

54.      Gillespie, P. G. and Beavo, J. A. (1988) Characterization of a Bovine Cone Photoreceptor Phosphodiesterase Purified by Cyclic GMP-sepharose Chromatography J. Biol. Chem . 263:8133-8141 .

55.      Beavo, J. A.  Multiple isozymes of cyclic nucleotide phosphodiesterase  (1988) Adv. Cyc. Nuc. and Prot. Phos. Res. 22:1-38 .

56.      Rapundolo, S. T., Lathrop, D. A., Harrison, S. A., Beavo, J. A., and Schwartz, A. (1988) Cyclic AMP-dependent and cyclic AMP-independent actions of a novel cardiotonic agent, OPC-8212.  Naunyn-Schmiedeberg's Arch Pharmacol. 338:692-698 .

57.      Blumenthal, D. K., Charbonneau, H., Edelman, A. E., Hinds, T. R., Rosenberg, G. B., Storm, D. R., Vincenzi, F. F., Beavo, J. A., and Krebs, E. G.  Synthetic peptides based on the calmodulin-binding domain of myosin light chain kinase inhibit activation of other calmodulin-dependent enzymes. Biochem. Biophys. Res. Comm. 156:860-865 (1988).

58.      Gillespie, P .G. and Beavo, J. A. (1989) Cyclic GMP is tightly bound to bovine retinal rod phosphodiesterase. Proc. Nat. Acad. Sci. USA  86:4311-4315 (1989).

59.      Gillespie, P. G., Prusti, R. K., Apel, E. D., and Beavo, J. A.  A soluble form of bovine rod phosphodiesterase has a novel 15-kDa subunit. J. Biol. Chem. 264:12187-12193 (1989).

60.      Stroop, S. D., Charbonneau, H., and Beavo, J. A. (1989) Direct photolabeling of allosteric and catalytic domains of the cGMP-stimulated cyclic nucleotide phosphodiesterase.  J. Biol. Chem. 264:13718-13725.

61.      Gillespie, P. G. and Beavo, J. A.  (1989) Inhibition and stimulation of photoreceptor phosphodiesterases by dipyridamole and M&B 22,948.  Mol. Pharm. 36:773-781.

62.      Novack, J.P., Charbonneau, H., Blumenthal. D.K., Walsh, K.A., and Beavo, J.A.  (1989) The domain structure of the calmodulin-dependent phosphodiesterase isozymes.  Calcium Protein Signaling, Editors: H. Hidaka, E. Carafoli, A.R. Means, and T. Tanaka Plenum Publishing Company, pp. 387-395.

63.      Charbonneau, H., Prusti, R. K., Trong, H. L., Sonnenburg, W. K., Mullaney, P. J., Walsh, K. A., and Beavo, J. A. (1990) Identification of a noncatalytic, cGMP-binding domain conserved in both the cGMP-stimulated and photoreceptor cyclic nucleotide phosphodiesterases.  Proc. Nat. Acad. Sci. USA 87:288-292.

64.      Beavo, J. A. and Reifsnyder, D. H. (1990) Primary sequence of cyclic nucleotide phosphodiesterase isozymes and the design of selective inhibitors.  TiPS 11:150-155.

65.      Le Trong, H., Beier, N. L., Sonnenburg, W. K., Stroop, S. D., Walsh, K. A., Beavo, J. A. and Charbonneau, H. (1990) Amino acid sequence of the cyclic GMP-stimulated phosphodiesterase from bovine heart.  Biochemistry 29:10280-10288.

66.      Watson, E. L., Singh, J. C., McPhee, C., Beavo, J. A., and Jacobson, K. L.  (1990) Evidence for a role of cGMP in cAMP metabolism in mouse parotid gland.  Mol. Pharm. 38:547-553.

67.      MacFarland, R. T. Stroop, S. D., and Beavo, J. A.  (1990)  Structural and Functional Characterization of Cyclic GMP-Stimulated Phosphodiesterases and Their Role in Intracellular Signal Transduction.  In Purines in Cellular Signaling: Targets for New Drugs.  K A. Jacobson, J.W. Daly, and V. Manganiello, Editors,  Springer-Verlag New York

68.      MacFarland, R.T., Zelus, B. D., and Beavo, J. A.  (1991) High concentrations of a cGMP-stimulated phosphodiesterase mediate ANP-induced decreases in cAMP and steroidogenesis in adrenal glomerulosa cells.  J. Biol. Chem. 266:136-142.

69.      Charbonneau, H., Kumar, S., Novack, J. P., Blumenthal, D.K., Griffin, P.R., Shabanowitz, J. J., Hunt, D.F., Beavo, J.A., and Walsh, K.A.  (1991) Evidence for domain organization within the 61 -kDa calmodulin-dependent cyclic nucleotide phosphodiesterase from bovine brain.  Biochemistry 30:7931-7940.

70.      Novack, J. P., Charbonneau, H., Walsh, K. A., and Beavo, J. A.  (1991) Sequence comparison of the 63, 61, and 59 kDa calmodulin-dependent cyclic nucleotide phosphodiesterases.  Biochemistry 30:7940-7947.

71.      Sonnenburg, W. K., Mullaney, P. J., and Beavo, J. A. (1991) Molecular cloning of a cGMP-stimulated cyclic nucleotide phosphodiesterase cDNA: Identification and distribution of isozyme variants.  J. Biol. Chem.  266:17655-17661.

72.      Stroop, S. D. and Beavo, J. A. (1991) Structure and function studies of the cGMP-stimulated phosphodiesterase.  J. Biol. Chem. 266:23802-23809.

73.      Bentley, J. K. and Beavo, J. A. (1992)  Regulation and function of cyclic nucleotides  Cur Opin. in Cell. Biol.  4: 233-240.

74.      Borisy, F. F., Ronnett, G. V., Cunningham, A. M., Julifs, D., Beavo, J.A., and Snyder, S. H. (1992) Calcium/calmodulin activated phosphodiesterase expressed in olfactory receptor neurons  J. Neuroscience. 12:915-923.

75.      Butt, E., Nolte, C. Schulz, S., Beltman, J., Beavo, J. A., Jastorff, B., and Walter, U. (1992) Analysis of the functional role of cGMP-dependent protein kinase in intact human platelets using a specific activator 8-pCPT-cGMP.  Biochem. Pharmacol. 43:2591-2600.

76.      Bentley, J. K., Kadlecek, A., Sonnenburg, W. K., Novack, J. P., Charbonneau, H., and Beavo, J. A. (1992) Molecular Cloning of cDNA Encoding a "63" kDa  Calmodulin-stimulated Phosphodiesterase from Bovine Brain. J. Biol. Chem. 267: 18676-18682.

77.      Sonnenburg, W. K., Segar, D., and Beavo, J. A. (1993)  Molecular cloning of a cDNA encoding the "61 kDa" calmodulin-stimulated cyclic nucleotide phosphodiesterase: tissue-specific expression of structurally related isoforms.  J. Biol. Chem. 268:645-652.

78.      Hamilton, S. E., Prusti, R. K., Bentley, J. K., Beavo, J. A. and Hurley, J. B. (1993)  Affinities of bovine photoreceptor cGMP phosphodiesterases for rod and cone inhibitory subunits. Febs Lett  318: 157-161.

79.      Michaeli, T., Bloom, T. J., Martins, T., Loughney, K., Ferguson, K., Riggs, M., Rogers. L., Beavo, J. A., and Wigler, M. (1993). Isolation and characterization of a previously undetected human cAMP phosphodiesterase by complementation of cAMP phosphodiesterase-deficient Saccharomyces cerevisiae.  J. Biol. Chem. 268:12925-12932.

80.      Chan, S. C. , Reifsnyder, D., Beavo, J. A., and Hanifin, J. M. (1993)  Immunochemical characterization of the distinct monocyte cyclic AMP-phosphodiesterase from patients with atopic dermatitis.  J. Allergy Clin. Immunol. 91:1179-1188.

81.      McAllister, L. M., Kadlecek, A. T., Sonnenburg, W. T., Seger, D., Francis, S. H., Thomas, M. K., Corbin, J. D. and  Beavo, J. A. (1993)   Isolation of a cDNA clone for the bovine lung cGMP-binding cGMP-specific phosphodiesterase. J. Biol. Chem. 268:22863-22873.

82.      Beltman, J., Sonnenburg, W. K., and Beavo, J. A. (1993)  The role of protein phosphorylation in the regulation of cyclic nucleotide phosphodiesterases. Molec. and Cell. Biochem. 127/128:239-253.

83.      Sonnenburg, W. K. and Beavo, J. A. (1994) Cyclic GMP and regulation of cyclic nucleotide hydrolysis.  Adv. in Pharmacol. 26:87-113.

84.      Yan, C., Bentley, J. K., Sonnenburg, W. K. & Beavo, J. A. (1994)   Differential expression of the 61 kDa and 63 kDa calmodulin-dependent phosphodiesterases in the mouse brain. J. Neuroscience  14:973-984.

85.      Florio, V. A., Sonnenburg, W. K., Johnson, R., Kwak, K., Jensen, G. S., Charbonneau, H., Walsh, K. A., and Beavo, J. A. (1994) Phosphorylation of the "61 kDa" calmodulin-stimulated cyclic nucleotide phosphodiesterase at serine 120 reduces its affinity for calmodulin.  Biochemistry  33:8948-8954.

86.      Beavo, J. A., Conti, M., and Heaslip, R. J. (1994) Multiple cyclic nucleotide phosphodiesterases. Molec. Pharmacol. 46:399-405

87.      Beltman, J., Becker, D. E., Butt, E., Jensen, G.S., Rybalkin S. D., Jastorff, B., and Beavo, J. A. (1995) Characterization of cyclic nucleotide phosphodiesterases with cyclic GMP analogs: topology of the catalytic domains.  Mol. Pharmacol. 47:330-339.

88.      Butt, E., Beltman, J., Becker, D. E., Jensen, G. S., Jastorff, B. and Beavo, J. A. (1995) Characterization of cyclic nucleotide phosphodisterases using cAMP analogs: the topology of the catalytic site and comparison to other cAMP-binding sites. Mol. Pharm. 47:340-347.

89.      Beavo, J. A. (1995) cGMP inhibition of heart phosphodiesterase: is it clinically relevant?  J. Clin. Investigation  95:445 .

90.      Villacres, E. C.  Wu, Z., Hua, W., Nielsen, M. D., Watters, J. J., Yan, C., Beavo, J. and Storm, D. R. (1995)  Developmentaly Expressed Ca2+ -sensitive adenylyl cyclase activity is disrupted in the brains of type I adenylyl cyclase mutant mice.  J. Biol. Chem.  270:14352-14357.

91.      Beavo, J. A. (1995) Cyclic nucleotide phosphodiesterases: functional implications of multiple isoforms.  Physiological Reviews  75:725-747.

92.      Yan, C., Bentley, J. K., Zhao, A., Loughney, K., and Beavo, J. A. (1995) Molecular cloning and characterization of a novel, high affinity calmodulin-dependent cyclic nucleotide phosphodiesterase selectively expressed in olfactory neurons.  PNAS 92:9677-9681

93.      McAllister-Lucas, L.M., T.L. Haik, J.L. Colbran, W.K. Sonnenburg, D. Seger, J. A. Beavo, and J. D. Corbin (1995) An essential aspartic acid at each of two allostric cGMP binding sites of a cGMP-specific phosphodiesterase. J. Biol. Chem.  270:30671-30679.

94.      Sonnenburg, W. K., Seger, D., Kwak, K. S., Huang, J., Charbonneau, H., Beavo, J. A. (1995) Identification of inhibitory and calmodulin-binding domains of the "59-kDa" and"61-kDa" calmodulin stimulated phosphodiesterases  J. Biol. Chem. 270:30989-31000.

95.      Loughney, K., Martins, T.J., Harris, E.A.S., Sadhu, K., Hicks, J.B., Sonnenburg, W.K., Beavo, J.A. and Ferguson, K. (1996) Isolation and characterization of cDNAs corresponding to two human calcium, calmodulin-regulated, 3',5' cyclic nucleotide phosphodiesterases: HSPDE1A and HSPDE1C.   J. Biol. Chem. 271:796-806.

96.      Bentley, J. K. and Beavo, J. A.  (1996) Role of multiple isozymes in the regulation of cyclic nucleotide synthesis and degradation.   Principles in Medical Biology. Cell Chemistry and Physiology: Part II. Edward Bittar and Neville Bittar Editors. JAI Press Greenwich, Inc.,  Greenwich, CT.p 77-121.

97.      Burns, F., Zhao, A. Z., and Beavo, J. A.  (1996)  Cyclic nucleotide phosphodiesterases: gene complexity, regulation by phosphorylation and physiological implications.  Adv. in Pharmacol. 36:29-48.

98.      Florio, S. K., Prusti, R. K., and Beavo, J. A. (1996) Solubilization of membrane bound rod phosphodiesterase by the rod phosphodiesterase delta subunit: structure, localization and function of the delta subunit.  J. Biol. Chem.  271:24036-24047.

99.      Yan, C., Zhao, A., Bentley, J. K., and Beavo, J. A. (1996) The calmodulin-dependent phosphodiesterase gene PDE1C encodes several functionally different splice variants in a tissue specific manner.  J. Biol. Chem. 271:25699-25706.

100.   Bloom, T. J. and Beavo, J.A. (1996) Identification and tissue specific expression of PDE7 phosphodiesterase splice variants.  Proc. Nat. Acad. Sci. USA 93:14188-14192.

101.   Rybalkin, S. D. and J. A. Beavo (1996). Multiplicity within cyclic nucleotide phosphodiesterases. Biochemical Society Transactions 24: 1005-1009.

102.   Zhao, A. Z., H. Zhao, J. Teague, W. Fugimoto and J. A. Beavo (1997). Attenuation of insulin secretion by IGF-1 is mediated through activation of phosphodiesterase 3B (PDE3B). Proc. Nat Acad. Sci. USA  94:3223-3228.

103.   Juilfs, D. W., Fulle, H. J., Zhao, A. Z., Houslay, M. D., Garbers, D. L., and Beavo, J. A. (1997) A subset of neurons that selectively express cGMP-stimulated phosphodiesterase (PDE2) and guanylyl cyclase-D define a unique olfactory signal transduction pathway.  Proc. Nat. Acad. Sci. USA 94:3388-3395.

104.   Rosman, G. J., Martins, T. J., Sonnenburg, W. K., Beavo, J. A,  Ferguson, K. and Loughney, K.  (1997) Isolation and characterization of human cDNAs encoding a cGMP-stimulated 3',5'-cyclic nucleotide phosphodiesterase. Gene 191:89-95.

105.   Yu, J., Wolda, S.L., Frazer, A.L.B., Florio, V.A., Martins, T.J., Snyder, P.B., Harris, E.A.S.,McDaw, K.N., Farrell, C.A., Steiner, B., Bentley, J.K., Beavo, J.A., Ferguson, K., Gelinas, R.  (1997)  Identification and characterization of a human calmodulin-stimulated phosphodiesterase PDE1B1  Cell. Signal. 9:519-529.

106.   Zhao, A. Z., Yan, C., Sonnenburg, W. K., and Beavo, J. A. (1997)  Recent advances in the study of Ca2+/CaM activated phosphodiesterases: expression and physiological functions.  Signal Transduction in Health and Disease 31:237-251.

107.   Rybalkin, S. D., Bornfeldt, K. E., Sonnenburg, W. K., Rybalkina, I. G., Kwak, K. S., Hansen, K., Krebs, E. G., and Beavo, J. A. (1997)  Calmodulin-stimulated cyclic nucleotide phosphodiesterase (PDE1C) is induced in human arterial smooth muscle cells of the synthetic, proliferative phenotype.  J. Clin. Invest.  100:2611-2621.

108.   Sonnenburg, W.K., Rybalkin, S.D., Bornfeldt, K.E. Kwak, K.S. Rybalkina, I.G. and Beavo, J.A. (1998) Identification , quantitation, and cellular localization of PDE1 calmodulin-stimulated cyclic nucleotide phosphodiesterases.  Methods: A companion to methods in enzymology. 14:3-19.

109.   Sonnenburg, W. K., G. A. Wayman, D. A. Storm and J. A. Beavo (1997). Cyclic nucleotide regulation by calmodulin. Calmodulin and signal transduction. San Diego, Academic Press. 237-286.

110.   Soderling, S.H., Bayuga, S.J., and Beavo, J.A. (1998)  Identification and characterization of a novel family of cyclic nucleotide phosphodiesterases. J. Biol. Chem. 273:15553-15558.

111.   Soderling, S.H. Bayuga, S.J., and Beavo, J.A. (1998)  Cloning and characterization of a novel cAMP specific cyclic nucleotide phosphodiesterase.  Proc. Nat. Acad. Sci.  95:8991-8996.

112.   Hanson, K.A., Burns, F., Rybalkin, S.D., Wager-Miller, J., Beavo, J.A. and Clarke, W. R. (1998) Developmental changes in lung cGMP phosphodiesterase-5 activity, protein, and message.  Am. J. Crit. Care Med.  158:279-288.

113.   Li, N., Florio, S.K., Pettenati, M.J., Nagesh-Rao, P., Beavo, J.A., and Baehr, W. (1998) Characterization of human and mouse rod cGMP phosphodiesterase gamma subunit (PDE6) and chromosomal localization of the human gene.  Genomics 49:76-82.

114.   Zhao, A.Z., Bornfeldt, K.E., and Beavo, J.A. (1998) Leptin inhibits insulin secretion by activation of phosphodiesterase 3B. J. Clin. Invest. 102:869-873.

115.   Wei, J, Zhao, A.Z., Chan, G.C., Baker, L.P., Impey, S, Beavo, J.A., and Storm, D. R.  (1998) Phosphorylation and inhibition of olfactory adenylyl cyclase by CaM kinase II in neurons: a mechanism for attenuation of olfactory signals.  Neuron 21:1-20.

116.   Loughney, K, Hill, T.R., Florio, V.A.. Uhler, L., Rosman, G.J. Wolda, S.L., Jones, B.A., Howard, M.L., McAllister-Lucas, L.M., Sonnenburg, W.K., Francis, S.H., Corbin, J.D., Beavo, J.A., Ferguson, K. (1998) Isolation and characterization of cDNAs encoding PDE5A, a human cGMP-binding, cGMP-specific 3’5’-cyclic nucleotide phosphodiesterase  Gene 216:139-147.

117.   Juilfs, D. M., Soderling, S., Burns, F., and Beavo, J.A. (1999) Cyclic GMP as substrate and regulator of cyclic nucleotide phosphodiesterases (PDEs). Reviews of Physiology Biochemistry and Pharmacology, 135:67-104 Springer Verlag.

118.   Li, L, Yee, C., and Beavo, J.A. (1999) CD3 and CD28 dependent induction of PDE7 required for T cell activation.  Science 283:848-851.

119.  Mou, H., Grazio, H.J., Cook, T.A., Beavo, J.A., and Cote, R.H. (1999)  cGMP binding to non catalytic sites on mammalian rod photoreceptor phosphodiesterase is regulated by binding of its g and d subunits. J. Biol. Chem. 274:18813-18820.

120.  Soderling, S.H., Bayuga, S.J., and Beavo, J.A. (1999) Isolation and characterization of a dual-substrate phosphodiesterase gene family: PDE10A.  Proc. Nat. Acad. Sci. USA 96:7071-7076.

121. Hetman J.M., Soderling S.H., Glavas N.A., Beavo J.A. (2000) Cloning and characterization of PDE7B, a cAMP-specific phosphodiesterase. Proc Natl Acad Sci U S A 97:472-476

122. Soderling, S.H. and Beavo, JA (2000) Regulation of cAMP and cGMP signaling: New Phosphodiesterases and New Functions. Cur. Opin. Cell Biol.12:174-179

123.  Zhao, A.Z., Shinohara, M.M., Huang, D., Shimizu, M., Eldar-Finkleman, H. Krebs, E.G., Beavo, J.A. and Bornfeldt, K.E. (2000) Leptin induces insulin-like signaling that antagonizes cAMP elevation by glucagon in hepatocytes. J. Biol. Chem. 275:11348-11354

124.  Fawcett, L., Baxendale, R., Stacey, P., McGrouther. C., Harrow, I., Soderling, S.H., Hetman, J.M., Beavo, J.A. and Phillips, S.C. (2000) Molecular cloning and characterization of a novel human phosphodiesterase gene family: PDE11A.  Proc. Nat. Acad. Sci. USA 97:3702-7

125.  Cook TA, and Beavo JA. (2000) Purification and assay of bovine type 6 photoreceptor phosphodiesterase and its subunits. Methods Enzymol. 315:597-616.

126. Sun Y, Li L, Lau F, Beavo JA, Clark EA.Infection of CD4⁺ memory T cells by HIV-1 requires expression of phosphodiesterase 4. J Immunol. 2000:1755-1761

127.  Hetman, JM, Robas, N., Baxendale. R., Fidock, M., Phillips, S.C., Soderling, S.H., Beavo, J.A. Cloning and characterization of two novel splice variants of human phosphodiesterase 11A. Proc. Nat. Acad. Sci.  2000 Nov 7;97(23):12891-5.

128.  Cook, TA, Ghomaschi, F, Gelb, MH, Florio, SK, and Beavo, JA.  Binding of the Delta Subunit to Rod Phosphodiesterase Catalytic Subunits Requires Methylated, Prenylated C-termini of the Catalytic Subunits.  Biochemistry. 2000 Nov 7;39(44):13516-23.

129.  Cook, TA, Ghomaschi, F, Gelb, MH, Florio, SK, and Beavo, JA. (2001) The delta subunit of type 6 phosphodiesterase reduces light-induced cGMP hydrolysis in rod outer segments.  J. Biol. Chem, Feb 16;276(7):5248-5255

130.  Yan, C. Zhao, A.Z., Sonnenburg, W.K., and Beavo, J.A. (2001)  Distinct spatial and temporal patterns of different Ca⁺⁺/calmodulin-stimulated phosphodiesterases in mouse testis.  Biology of Reproduction  64:1746-1754

131.  Shimizu-Albergine, M., Ippolito, D, and Beavo, JA. (2001) Down-regulation of fasting-induced CRE-mediated gene induction by leptin in neuropeptide Y neurons of the arcuate nucleus J. Neuro Sci, Feb 15;21(4):1238-1246

132.  Glavas NA, Ostenson C, Schaefer JB, Vasta V, Beavo JA. (2001) T cell activation up-regulates cyclic nucleotide phosphodiesterases 8A1 and 7A3.  Proc Natl Acad Sci U S A May 22;98:6319-24

133.  Kim D, Rybalkin SD, Pi X, Wang Y, Zhang C, Munzel T, Beavo JA, Berk BC, Yan C.  (2001) Upregulation of phosphodiesterase 1A1 expression is associated with the development of nitrate tolerance.  Circulation  Nov 6;104:2338-43

134.  Rascón, A., Soderling. SH. and Beavo, JA. (2002) Cloning and characterization of a cAMP-specific phosphodiesterase (TbPDE2B) from Trypanosoma brucei. Proc Natl Acad Sci U S A. Apr 2;99(7):4714-4719.

135.  Rybalkin SD, Rybalkina I, Beavo JA, Bornfeldt KE. (2002) Cyclic nucleotide phosphodiesterase 1C promotes human arterial smooth muscle cell proliferation. Circ Res.  Feb 8;90(2):151-7

136.  Rybalkin SD, Rybalkina IG, Feil R, Hofmann F, Beavo JA. (2002)  Regulation of cGMP-specific phosphodiesterase (PDE5) phosphorylation in smooth muscle cells.  J Biol Chem. 2002 Feb 1;277(5):3310-7.

137.  Martinez, Sergio, E.,  Albert Wu, Natalie A. Glavas, Xiao-Bo Tang, Stewart Turley, Wim G. J. Hol, and Joseph A. Beavo  (2002) The Two GAF Domains in Phosphodiesterase 2A Have Distinct Roles in Dimerization and in cGMP Binding.  PNAS Oct 1 99:13260-13265.

138.  Martinez, SE, Beavo, JA, and Hol, WGJ  “GAF domains: two billion year old swithces that bind cyclic nucleotides”.  Molecular Interventions Sept 2002 2:317-323

139.  Beavo JA, Brunton LL. Timeline: Cyclic nucleotide research #151; still expanding after half a century.  Nat Rev Mol Cell Biol. 2002 Sep;3(9):710-8.

140.  Muradov, KG, Boyd, KK, Martinez, SE, Beavo, JA, and Artemyev, NO. (2002) The GAFa domains of rod cGMP-phosphodiesterase 6 determine the selectivity of the enzyme dimerization.  J Biol Chem. 2003 Mar 21;278(12):10594-601

141.  Rybalkin SD, Rybalkina IG, Shimizu-Albergine M, Tang XB, Beavo JA. PDE5 is converted to an activated state upon cGMP binding to the GAF A domain.  EMBO J. 2003 Feb 3;22(3):469-78.

142.  Shimizu-Albergine, M, Rybalkin, SD, Rybalkina, IG, Feil, R, Wolfsgruber, W^. ,Hofmann, F and Beavo, JA (2003) Individual cerebellar Purkinje cells express different cGMP PDEs: in vivo phosphorylation of cGMP-specific PDE (PDE5) as an indicator of PKG activation.  J. Neuroscience July 23; vol 23:6452-6459.

143.  Rybalkin^, SD, Yan^. C, Bornfeldt, KE and Beavo, JA.  (2003) Cyclic GMP Phosphodiesterases and Regulation of Smooth Muscle Function. Circ Res 93:280-291.

144. van Staveren WC, Glick J, Markerink-van Ittersum M, Shimizu M, Beavo JA, Steinbusch HW, de Vente J. Cloning and localization of the cGMP-specific phosphodiesterase type 9 in the rat brain.  J Neurocytol. 2002 Sep-Nov;31(8-9):729-41.

145. Giordano, D, Magaletti, D.M, Clark, E.A., Beavo, JA Cyclic nucleotides promote monocyte differentiation towards a DC-SIGN⁺ (CD209) intermediate cell and impair differentiation into dendritic cells.  J. Immunol  2003 Dec 15;171(12):6421-30

146. Van Staveren WC, Steinbusch HW, Markerink-Van Ittersum M, Repaske DR, Goy MF, Kotera J, Omori K, Beavo JA, De Vente J.  mRNA expression patterns of the cGMP-hydrolyzing phosphodiesterases types 2, 5, and 9 during development of the rat brain.  J Comp Neurol. 2003 Dec 22;467(4):566-80.

 147. Bender, AT, Ostenson, C L, Giordano, D., Beavo, J.A. Different types of macrophages express Unique Phosphodiesterases, Cell Signaling, 2004 Mar;16(3):365-74

 148. Wu AY, Tang XB, Martinez SE, Ikeda K, Beavo JA.  Molecular determinants for cyclic nucleotide binding to the regulatory domains of phosphodiesterase 2A.  J Biol Chem. 2004 Sep 3;279(36):37928-38.

 149. Huang D, Hinds TR, Martinez SE, Doneanu C, Beavo JA. Molecular determinants of cGMP-binding to chicken cone photoreceptor phosphodiesterase  J Biol Chem. 2004 Nov 12; 279(46):48143-51.

 150. Bender AT, Beavo JA.  Specific localized expression of cGMP PDEs in Purkinje neurons and macrophages.  Neurochem Int. 2004 Nov;45(6):853-57.

 151. Asirvatham AL, Galligan SG, Schillace RV, Davey MP, Vasta V, Beavo JA, Carr DW.  (2004) A-kinase anchoring proteins interact with phosphodiesterases in T lymphocyte cell lines.  J. Immunol. Oct 15;173(8)4806-14.

 152. Laxman S, Rascon A, Beavo JA.  Trypanosome cyclic nucleotide phosphodiesterase 2B binds cAMP through its GAF-A domain.  J Biol Chem.  2005 Feb 4; 280(5):3771-9.

 153. Bender AT, Ostenson CL, Wang EH, Beavo JA. (2005) Selective up-regulation of PDE1B2 upon monocyte-to-macrophage differentiation.  Proc Natl Acad Sci U S A.  Jan 11;102(2):497-502.

 154. Martinez SE, Bruder S, Schultz A, Zheng N, Schultz JE, Beavo JA, Linder JU.  (2005) Crystal structure of the tandem GAF domains from a cyanobaterial adenylyl cyclase: Modes of ligand binding and dimerization.  Proc Natl Acad Sci U S A.  2005 Feb 22  102(8):3082-3087.

 155. Bruder S, Linder JU, Martinez SE, Zheng N, Beavo JA, Schultz JE. (2005) The cyanobacterial tandem GAF domains from the cyaB2 adenylyl cyclase signal via both camp-binding sites.  Proc Natl Acad Sci U S A. Feb 22, 102(8):3088-3092

 156. Vasta V, Sonnenburg WK, Yan C, Soderling SH, Shimizu-Albergine M, Beavo JA.  Identification of a New Variant of PDE1A Calmodulin-Stimulated Cyclic Nucleotide Phosphodiesterase Expressed in Mouse Sperm. Biol Reprod. (2005) Oct;73(4):598-609

 157. Kunz, S., Beavo, JA, Kunz S, Beavo JA, D'Angelo MA, Flawia MM, Francis SH, Johner A, Laxman S, Oberholzer M, Rascon A, Shakur Y, Wentzinger L, Zoraghi R, Seebeck T. Cyclic nucleotide specific phosphodiesterases of the kinetoplastida: a unified nomenclature. Mol Biochem Parasitol. 2006 Jan;145(1):133-5.

 158.  Bender, AT., Beavo, JA., PDE1B2 regulates cGMP and a subset of the phenotypic characteristics acquired upon macrophage differentiation from a monocyte.  Proc Nat Acad Sci USA (2006) Jan 10; 103:460-465

 159.  Bender, AT and Beavo, JA.,  Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use.  Pharmacological Reviews 2006 Sep;58(3):488-520

 160.  Díaz-Benjumea^, R., Laxman^, S., Hinds^, TR., Beavo^, JA., and Rascón^, A  Characterization and comparison of cAMP specific cyclic nucleotide phosphodiesterase activities and GAF domain-cAMP binding properties of TcrPDEB1 and TcrPDEB2 from Trypanosoma cruzi  2006  Biochem J. Sep;58(3):488-520.

 161.   Laxman^, S, Riechers^. A., Sadilek^, M., Schwede^, F and Beavo, JA.  Hydrolysis Products of cAMP Analogs Cause Transformation of T. brucei from Slender to Stumpy-Like forms. Proc. Nat. Acad. Sci. USA 103:19194-99 (2006).

 162.  Vasta, V., Shimizu-Albergine, M., and Beavo, JA. Modulation of Leydig cell function by PDE8A.  Proc. Nat. Acad. Sci. 103:19925-30 (2006). 

 163.  Bender, AT, Beavo, JA  Cyclic nucleotide phosphodiesterases:molecular regulation to clinical use.  Pharmacol Rev  58:488-520 (2006)

 164.  Gavin MA, Rasmussen JP, Fontenot JD, Vasta V, Manganiello VC, Beavo JA, Rudensky AY. FoxP3-dependent programme of regulatory T-cell differentiation Nature 2007 Feb 15;445(7129):771-5.  PMID: 17220874

 165.  Askari B, Kanter JE, Sherrid AM, Golej DL, Bender AT, Liu J, Hsueh WA, Beavo JA, Coleman RA, Bornfeldt KE.  Rosiglitazone Inhibits Acyl-CoA Synthetase Activity and Fatty Acid Partitioning to Diacylglycerol and Triacylglycerol via a PPAR{gamma}-Independent Mechanism in Human Arterial Smooth Muscle Cells and Macrophages. Diabetes. 2007 Apr;56(4):1143-52. PMID: 17259370

 166.        Conti, M and Beavo, J.  Biochemistry and Physiology of Cyclic Nucleotide Phosphodiesterases: Essential Components in Cyclic Nucleotide Signaling. Annu Rev Biochem. (2007) 76:481-511  Mar 21. PMID: 17376027

 167.        Surapisitchat, J. Jeon, KI, Yan, C., and Beavo JA. Differential Regulation of Endothelial Cell Permeability by cGMP via Phosphodiesterases 2 and 3. Circ Res. (2007) 101(8):811-8. PMID: 17704206

 168.        Laxman, S. and Beavo, JA.  Cyclic nucleotide signaling mechanisms in trypanosomes: possible targets for therapeutic agents.  Mol Interv. 2007 Aug;7(4):203-15. PMID: 17827441

 169.        Kass, D.A., Champion, H.C., and Beavo, J.A. Phosphodiesterase type 5: expanding roles in cardiovascular regulation. Circ Res. 2007 Nov 26;101(11):1084-95. PMID: 18040025

 170.        Heikaus CC, Stout JR, Sekharan MR, Eakin CM, Rajagopal P, Brzovic PS, Beavo JA, Klevit RE.  Solution structure of the cGMP binding GAF domain from phosphodiesterase 5: Insights into nucleotide specificity, dimerization, and cGMP-dependent conformational change.  J Biol Chem. (2008) 283(33):22749-59. PMID: 18534985       

171.        Poppe H, Rybalkin SD, Rehmann H, Hinds TR, Tang XB, Christensen AE, Schwede F, Genieser HG, Bos JL, Doskeland SO, Beavo JA, Butt E.  Cyclic nucleotide analogs as probes of signaling pathways.  Nat Methods. 2008 Apr;5(4):277-8. PMID: 18376388

172.         Martinez SE, Heikaus CC, Klevit RE, Beavo JA. The structure of the GAF A domain from PDE 6C reveals determinants of cGMP-binding, a conserved binding surface, and a large cGMP-dependent conformational change. J Biol Chem. (2008) 283(38):25913-9. PMID: 18614542

173.        Sergio E. Martinez, Clemens C. Heikaus and Joseph A. Beavo, Cyclic Nucleotide-Binding GAF Domains in Phosphodiesterases and Adenylyl Cyclases. In: Ralph A. Bradshaw and Edward A. Dennis, editors, Handbook of Cell Signaling 2nd edition. Oxford: Academic Press, 2009, pp. 1531-1536. ISBN: 978-0-12-374145-5 © Copyright 2009 Elsevier Inc. Academic Press.

 174.        James Surapisitchat, Joseph A. Beavo, Phosphodiesterase Families. In: Ralph A. Bradshaw and Edward A. Dennis, editors, Handbook of Cell Signaling 2nd edition. Oxford: Academic Press, 2009, pp. 1409-1414. ISBN: 978-0-12-374145-5 © Copyright 2009 Elsevier Inc. Academic Press.

 175.        Miller CL, Oikawa M, Cai Y, Wojtovich AP, Nagel DJ, Xu X, Xu H, Florio V, Rybalkin SD, Beavo JA, Chen YF, Li JD, Blaxall BC, Abe JI, Yan C.  Role of Ca2+/Calmodulin-Stimulated Cyclic Nucleotide Phosphodiesterase 1 in Mediating Cardiomyocyte Hypertrophy. Circ Res. 2009 Sep 24.

 176.        Hertz, AL, Bender, AT, Smith, KC, Gilchrist, M, Amieux, PS, Aderem, A, Beavo, JA.  Elevated cyclic AMO and PDE4 inhibition induce chemokine expression in human monocyte-derived macrophages.  Proc Natl Acad Sci USA. 106:21978-83 2009 PMID 19959669.

177.        Lukowski R, Rybalkin, SD, Loga F, Leiss V, Beavo, JA, and Hofmann, F. Cardiac hypertrophy is not amplified by deletion of cGMP-dependent protein kinase I in cardiomyocytes.  Proc Natl Acad Sci 107:5646-51  2010 PMID 20212138.

178.        Patrucco, E, Albergine MS, Santana, LF, and Beavo, JA.  Phosphodiesterase 8A (PDE*A) Regulates Excitation-Contraction Coupling in Ventricular Myocytes.  J Mol Cell Cardiol 2010 Mar 27  (epub ahead of print) PMID 2035094.

Brief Summary of Research Program

 

            Dr. Beavo's research group investigates the role of cyclic nucleotide phosphodiesterases (PDEs) in controlling the amplitude and duration of cyclic AMP and cyclic GMP signaling pathways.  There are a large number of different isozyme families of PDEs that are differentially regulated by drugs and hormones.  Many were first discovered and studied in this laboratory.  Included among the agents that regulate PDEs are insulin, glucagon, EDRF and many neurotransmitters.  Much of our recent work has been to determine the physiological reasons for the existence of so many isozymes and to understand mechanistically how they function.  In order to understand the mechanisms by which different phosphodiesterases are regulated and influence cyclic AMP and cyclic GMP, several different general approaches have been and are being used.  The first involves identification, expression or isolation of individual isozyme of phosphodiesterase present in different mammalian tissues.  The structural, functional, and kinetic properties of the isolated isozymes are then characterized.  A second and related approach has been to develop isozyme specific probes to each phosphodiesterase and utilize them to study localization, function and regulation in crude systems and in intact cells.  These include monoclonal antibodies, antisense mRNAs, siRNA, and various drugs.  An important new area of research is to develop methods for studying PDE function in specific sub-regions of the cell.  Finally, deletion and mutagenesis analysis, analysis of dominant-negative mutants, and reconstitution studies with the expressed products is often used to determine function.  More recently we have also initiated gene disruption studies as a mechanism of determining function.  Taken together these approaches have yielded at least a partial understanding of the structure, regulation and function of these enzymes in the cell.  Particular systems of current interest include the roles of PDEs in inflammation, pulmonary vascular function, cardiac hypertrophy, insulin secretion, and steroidogenesis.  We also have a major project on the role of cyclic nucleotides and PDE inhibitors in muscular dystrophy.