Research Topics
Genomes and Genes
Species | Marco ContiSummaryAffiliation: Stanford University Country: USA Publications
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Publications
Specificity of the cyclic adenosine 3',5'-monophosphate signal in granulosa cell functionMarco Conti
Division of Reproductive Biology, Department of Gynecology and Obstetrics, Stanford University School of Medicine, California 94305, USA
Biol Reprod 67:1653-61. 2002..It is hoped this compendium will provide a framework with which to understand how the initial signals activated by gonadotropins control the complex patterns of gene expression that are required for follicle maturation and ovulation...
Role of cyclic nucleotide signaling in oocyte maturationMarco Conti
Division of Reproductive Biology, Department of Gynecology and Obstetrics, Stanford University School of Medicine, Stanford, CA 94305, USA
Mol Cell Endocrinol 187:153-9. 2002..Thus, PDE3 plays an essential role in the signaling pathway that controls resumption of meiosis in amphibians and mammals. Understanding the regulation of this enzyme may shed some light on the signals that trigger oocyte maturation...
Role of the epidermal growth factor network in ovarian folliclesMarco Conti
Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California 94305 5317, USA
Mol Endocrinol 20:715-23. 2006..This model has important implications for ovarian physiology and for the development of new strategies for the pharmacological control of ovulation and for gamete maturation in vitro...
Biochemistry and physiology of cyclic nucleotide phosphodiesterases: essential components in cyclic nucleotide signalingMarco Conti
Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California 943095 5317, USA
Annu Rev Biochem 76:481-511. 2007....
Cyclic AMP-specific PDE4 phosphodiesterases as critical components of cyclic AMP signalingMarco Conti
Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California 94305, USA
J Biol Chem 278:5493-6. 2003
EGF-like growth factors as mediators of LH action in the ovulatory follicleJy Young Park
Division of Reproductive Biology and Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA 94305, USA
Science 303:682-4. 2004..Thus, these EGF-related growth factors are paracrine mediators that propagate the LH signal throughout the follicle...
Luteinizing hormone signaling in preovulatory follicles involves early activation of the epidermal growth factor receptor pathwaySara Panigone
Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford, University School of Medicine, Stanford, California 94305, USA
Mol Endocrinol 22:924-36. 2008..Thus, complex mechanisms are involved in the rapid amplification and propagation of the LH signal within preovulatory follicles and include the early activation of the EGF network...
Luteinizing hormone-dependent activation of the epidermal growth factor network is essential for ovulationMinnie Hsieh
Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305 5317, USA
Mol Cell Biol 27:1914-24. 2007....
Protein kinase B/Akt phosphorylation of PDE3A and its role in mammalian oocyte maturationSeung Jin Han
Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University, 300 Pasteur Drive, Stanford, CA 94305, USA
EMBO J 25:5716-25. 2006..Collectively, these data indicate that activation of PDE3A by PKB/Akt-mediated phosphorylation plays a role in the control of PDE3A activity in mammalian oocytes...
Specific role of phosphodiesterase 4B in lipopolysaccharide-induced signaling in mouse macrophagesS L Catherine Jin
Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA 94305, USA
J Immunol 175:1523-31. 2005..Moreover, they provide proof of concept that a PDE4 inhibitor with subtype selectivity retains useful pharmacological effects...
The oligomerization state determines regulatory properties and inhibitor sensitivity of type 4 cAMP-specific phosphodiesterasesWito Richter
Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California 94305 5317, USA
J Biol Chem 279:30338-48. 2004..Taken together, our data indicate that dimerization defines the properties of PDE4 enzymes and suggest a common structural and functional organization for all PDEs...
Generation of mouse oocytes defective in cAMP synthesis and degradation: endogenous cyclic AMP is essential for meiotic arrestSergio Vaccari
Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University, CA 94305, USA
Dev Biol 316:124-34. 2008..These findings also suggest that cAMP diffusion through gap junctions or the activity of additional receptors is not sufficient by itself to maintain the meiotic arrest in the mouse oocyte...
The G-protein-coupled receptors GPR3 and GPR12 are involved in cAMP signaling and maintenance of meiotic arrest in rodent oocytesMary Hinckley
Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305 5317, USA
Dev Biol 287:249-61. 2005..We propose that the cAMP levels required for maintaining meiotic arrest in mouse and rat oocytes are dependent on the expression of Gpr3 and/or Gpr12...
Nonredundant function of phosphodiesterases 4D and 4B in neutrophil recruitment to the site of inflammationMiyako Ariga
Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA 94305, USA
J Immunol 173:7531-8. 2004..These data demonstrate that PDE4B and PDE4D play complementary, but not redundant, roles in the control of neutrophil function...
Rodent oocytes express an active adenylyl cyclase required for meiotic arrestKathleen Horner
Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University, Stanford, CA 94305, USA
Dev Biol 258:385-96. 2003..Collectively, these data provide evidence that an adenylyl cyclase is functional in rodent oocytes and that its activity is involved in the control of oocyte meiotic arrest...
Phosphodiesterase regulation is critical for the differentiation and pattern of gene expression in granulosa cells of the ovarian follicleJy Young Park
Division of Reproductive Biology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, California 94305 5317, USA
Mol Endocrinol 17:1117-30. 2003....
Splice variants of the cyclic nucleotide phosphodiesterase PDE4D are differentially expressed and regulated in rat tissueWito Richter
Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA 94305 5317, USA
Biochem J 388:803-11. 2005..As PDE4 inhibitors have different affinities for distinct PDE4D splicing variants, our results indicate that a better definition of the pattern of PDE4 expression is required for target validation...
PDE4D plays a critical role in the control of airway smooth muscle contractionCeline Mehats
Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, 300 Pasteur Dr, Room A344, Stanford, California 94305 5317, USA
FASEB J 17:1831-41. 2003..These results demonstrate that PDE4D plays a key role in balancing relaxant and contracting cues in airway smooth muscle, suggesting that natural mutations in the PDE4D gene have profound effects on airway tone...
New pathways from PKA to the Cdc2/cyclin B complex in oocytes: Wee1B as a potential PKA substrateSeung Jin Han
Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California 94305, USA
Cell Cycle 5:227-31. 2006..As as result of these regulatory loops, the Cdc2/cyclin B complex is maintained in an inactive state by the two-way PKA-dependent activation of Wee1 and inactivation of Cdc25...
Lack of functional pregnancy-associated plasma protein-A (PAPPA) compromises mouse ovarian steroidogenesis and female fertilityMette Nyegaard
Department of Ob Gyn, Stanford University School of Medicine, Stanford, CA, USA
Biol Reprod 82:1129-38. 2010..Taken together, these data demonstrate an important role of PAPPA in modulating ovarian function and female fertility by control of the bioavailability of ovarian IGF...
Soluble adenylyl cyclase (sAC) is indispensable for sperm function and fertilizationFang Xie
Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA 94305, USA
Dev Biol 296:353-62. 2006..These findings demonstrate that sAC plays a critical role in cAMP signaling in spermatozoa and that defective cAMP production prevents engagement of multiple components of capacitation resulting in male infertility...
Phosphodiesterase 4D is required for beta2 adrenoceptor subtype-specific signaling in cardiac myocytesYang Xiang
Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA
Proc Natl Acad Sci U S A 102:909-14. 2005..They also illustrate a mechanism for fine-tuned betaAR subtype signaling specificity and intensity in the cardiac system...
Signaling from beta1- and beta2-adrenergic receptors is defined by differential interactions with PDE4Wito Richter
Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA 94305 5317, USA
EMBO J 27:384-93. 2008....
Potential role of protein tyrosine phosphatase nonreceptor type 13 in the control of oocyte meiotic maturationTaku Nedachi
Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA 94305, USA
Development 131:4987-98. 2004..These findings indicate that PTPN13 is involved in the regulation of the meiotic cell cycle...
Wee1B is an oocyte-specific kinase involved in the control of meiotic arrest in the mouseSeung Jin Han
Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University, Stanford, California 94305, USA
Curr Biol 15:1670-6. 2005..Thus, mWee1B is a key MPF inhibitory kinase in mouse oocytes, functions downstream of PKA, and is required for maintaining meiotic arrest...
Expression of the soluble adenylyl cyclase during rat spermatogenesis: evidence for cytoplasmic sites of cAMP production in germ cellsFang Xie
Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA 94305-5317, USA
Dev Biol 265:196-206. 2004..These findings indicate that cAMP production in spermatids and spermatozoa may occur at sites other than the plasma membrane and suggest that full-length sAC may play a role during spermatid differentiation...
The mouse polyubiquitin gene Ubb is essential for meiotic progressionKwon Yul Ryu
Department of Biological Sciences, Bio X Program, Stanford University, Stanford, California 94305, USA
Mol Cell Biol 28:1136-46. 2008....
Protein kinase B/Akt is essential for the insulin- but not progesterone-stimulated resumption of meiosis in Xenopus oocytesCarsten B Andersen
Division of Reproductive Biology, Department of Gynecology and Obstetrics, Stanford University School of Medicine, Stanford, CA 94305, U S A
Biochem J 369:227-38. 2003..These data demonstrate a crucial role for Akt in the insulin-stimulated cell cycle progression of Xenopus oocytes, whereas Akt may have an ancillary function in progesterone signalling...
Calcium regulation of the soluble adenylyl cyclase expressed in mammalian spermatozoaBijay S Jaiswal
Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA 94305 5317, USA
Proc Natl Acad Sci U S A 100:10676-81. 2003....
Cyclic nucleotide phosphodiesterases and their role in endocrine cell signalingCeline Mehats
Division of Reproductive Biology, Dept Gynecology and Obstetrics, Stanford University School of Medicine, 300 Pasteur Drive, Room A344, Stanford, CA 94305-5317, USA
Trends Endocrinol Metab 13:29-35. 2002..This review explores the involvement of PDEs in the regulation of intracellular signaling and focuses on the known and potential roles that are of interest to endocrinologists...
G-protein-coupled receptor signaling and the EGF network in endocrine systemsMinnie Hsieh
Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University, Stanford, CA 94305-5317, USA
Trends Endocrinol Metab 16:320-6. 2005..Recent observations from the pituitary and in the ovary are providing new insight into the role of this network in endocrine systems...
Induction of the cyclic nucleotide phosphodiesterase PDE4B is essential for LPS-activated TNF-alpha responsesS L Catherine Jin
Division of Reproductive Biology, Department of Gynecology and Obstetrics, Stanford University School of Medicine, Stanford, CA 94305 5317, USA
Proc Natl Acad Sci U S A 99:7628-33. 2002..These findings demonstrate that PDE4B gene activation by LPS constitutes a feedback regulation essential for an efficient immune response...
Generation of PDE4 knockout mice by gene targetingS-L Catherine Jin
Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University Medical Center, CA, USA
Methods Mol Biol 307:191-210. 2005..In this chapter, we describe the basic protocols used to generate the PDE4 knockout mice...
Dimerization of the type 4 cAMP-specific phosphodiesterases is mediated by the upstream conserved regions (UCRs)Wito Richter
Division of Reproductive Biology, Department of Gynecology and Obstetrics, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305-5317, USA
J Biol Chem 277:40212-21. 2002..Therefore, dimerization of the long PDE4 forms may be an additional function of the UCR domains that further explains differences in the regulatory properties between the long and short PDE4 splice variants...
Soluble adenylyl cyclase is not required for axon guidance to netrin-1Simon W Moore
Centre for Neuronal Survival, Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada H3A 2B4
J Neurosci 28:3920-4. 2008..Therefore, although cAMP can alter the response of axons to netrin-1, we conclude that netrin-1 does not alter cAMP levels in axons attracted by this cue, and that sAC is not required for axon attraction to netrin-1...
Targeting of cyclic AMP degradation to beta 2-adrenergic receptors by beta-arrestinsStephen J Perry
Howard Hughes Medical Institute, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
Science 298:834-6. 2002....
Cellular mechanisms underlying prostaglandin-induced transient cAMP signals near the plasma membrane of HEK-293 cellsThomas C Rich
Department of Pharmacology, College of Medicine and Center for Lung Biology, University of South Alabama, Mobile, AL 36688, USA
Am J Physiol Cell Physiol 292:C319-31. 2007..This model has allowed us to quantitatively demonstrate the importance of PKA-mediated stimulation of PDE4 activity in shaping near-membrane cAMP signals...
A view into the catalytic pocket of cyclic nucleotide phosphodiesterasesMarco Conti
Nat Struct Mol Biol 11:809-10. 2004
Cyclic nucleotide phosphodiesterase 3A-deficient mice as a model of female infertilitySilvia Masciarelli
Pulmonary Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland 20892, USA
J Clin Invest 114:196-205. 2004..Pde3a(-/-) mice represent an in vivo model where meiotic maturation and ovulation are dissociated, which underscores inhibition of oocyte maturation as a potential strategy for contraception...
Mice deficient for soluble adenylyl cyclase are infertile because of a severe sperm-motility defectGloria Esposito
Department of Pharmacology and Lead Discovery Unit, NV Organon, P O Box 20, 5340 BH, Oss, The Netherlands
Proc Natl Acad Sci U S A 101:2993-8. 2004..The crucial role of sAC in fertility and the absence of any other obvious pathological abnormalities in sAC-deficient mice may provide a rationale for developing inhibitors that can be applied as a human male contraceptive...
A specific pattern of phosphodiesterases controls the cAMP signals generated by different Gs-coupled receptors in adult rat ventricular myocytesFrancesca Rochais
INSERM, U769, , France
Circ Res 98:1081-8. 2006..These results identify specific functional coupling of individual PDE families to Gs-coupled receptors as a major mechanism enabling cardiac cells to generate heterogeneous cAMP signals in response to different hormones...
Critical role of PDE4D in beta2-adrenoceptor-dependent cAMP signaling in mouse embryonic fibroblastsMatthew D Bruss
Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, California 94143, USA
J Biol Chem 283:22430-42. 2008..Finally, PDE4D ablation affected the kinetics of beta2AR desensitization as well as the interaction of the receptor with Galphai. These findings demonstrate that PDE4D plays a major role in shaping the beta2AR signal...
PDE4B polymorphisms and decreased PDE4B expression are associated with schizophreniaS Hossein Fatemi
Department of Psychiatry, University of Minnesota Medical School, MMC 392, Minneapolis, MN 55455, USA
Schizophr Res 101:36-49. 2008....
Spatiotemporal dynamics of beta-adrenergic cAMP signals and L-type Ca2+ channel regulation in adult rat ventricular myocytes: role of phosphodiesterasesJérôme Leroy
INSERM U 769, Universite Paris Sud 11, Faculte de Pharmacie, 5, rue J B Clement, F 92296 Chatenay Malabry Cedex, France
Circ Res 102:1091-100. 2008..These results reveal temporally distinct beta-adrenergic receptor cAMP compartments in ARVMs and shed new light on the intricate roles of PDE3 and PDE4...
Regulation of cAMP-specific phosphodiesterases type 4B and 4D (PDE4) splice variants by cAMP signaling in primary cortical neuronsCarrol D'Sa
Laboratory of Molecular Psychiatry, Departments of Psychiatry and Pharmacology, Yale University School of Medicine, Connecticut Mental Health Center, 34 Park Street, New Haven, CT 06508, USA
J Neurochem 81:745-57. 2002..These data demonstrate that in cortical neurons, a short PDE4B2 intronic promoter is regulated by CREB, confers cAMP responsitivity and directs PDE4B2 mRNA and protein expression...
Phosphodiesterase 4D forms a cAMP diffusion barrier at the apical membrane of the airway epitheliumAnthony P Barnes
Department of Cell and Developmental Biology and Cystic Fibrosis Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
J Biol Chem 280:7997-8003. 2005..These findings underscore the concept that subcellular localization of individual PDE isozymes is an important mechanism for confining cAMP signaling to functional domains within cells...
Lowering cyclic adenosine-3',5'-monophosphate (cAMP) levels by expression of a cAMP-specific phosphodiesterase decreases intrinsic pulsatile gonadotropin-releasing hormone secretion from GT1 cellsHiroshi Yoshida
Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, San Francisco, California 94143, USA
Mol Endocrinol 17:1982-90. 2003..Genetically targeted expression of PDE4D1 represents a powerful approach to study the role of cAMP levels in specific populations of neurons in transgenic animals...
Anxiogenic-like behavioral phenotype of mice deficient in phosphodiesterase 4B (PDE4B)Han Ting Zhang
Department of Behavioral Medicine and Psychiatry, West Virginia University Health Sciences Center, Morgantown, WV 26506, USA
Neuropsychopharmacology 33:1611-23. 2008..Taken together, these results suggest that the PDE4B subfamily is involved in signaling pathways that contribute to anxiogenic-like effects on behavior...
AKAP3 selectively binds PDE4A isoforms in bovine spermatozoaMalini Bajpai
Department of Medicine, Oregon Health and Sciences University and VA Medical Center, Portland, OR 97239, USA
Biol Reprod 74:109-18. 2006..These data suggest that AKAP3 binds both PKA and PDE4A and functions as a scaffolding protein in spermatozoa to regulate local cAMP concentrations and modulate sperm functions...
Dynamic regulation of cystic fibrosis transmembrane conductance regulator by competitive interactions of molecular adaptorsJi Hyun Lee
Department of Pharmacology, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 120 752, Korea
J Biol Chem 282:10414-22. 2007....
Phosphodiesterase 4D deficiency in the ryanodine-receptor complex promotes heart failure and arrhythmiasStephan E Lehnart
Clyde and Helen Wu Center for Molecular Cardiology, Department of Physiology and Cellular Biophysics, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA
Cell 123:25-35. 2005..These data suggest that reduced PDE4D activity causes defective RyR2-channel function associated with heart failure and arrhythmias...
Phosphodiesterase expression targeted to gonadotropin-releasing hormone neurons inhibits luteinizing hormone pulses in transgenic ratsSreenivasan Paruthiyil
Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, CA 94143, USA
Proc Natl Acad Sci U S A 99:17191-6. 2002..The GPR-4 line of transgenic rats provides a genetic model for the understanding of the role of pulsatile gonadotropin release in follicular development...
IGF-I-induced differentiation of L6 myogenic cells requires the activity of cAMP-phosphodiesteraseVania De Arcangelis
Dipartimento di Istologia ed Embriologia Medica, , 00161 Roma, Italia
Mol Biol Cell 14:1392-404. 2003..These results show that downregulation of cAMP signaling through cAMP-phosphodiesterase stimulation is a prerequisite for induction of myogenesis...
Antidepressant-like profile and reduced sensitivity to rolipram in mice deficient in the PDE4D phosphodiesterase enzymeHan Ting Zhang
Department of Pharmacology, University of Tennessee Health Science Center, Memphis, TN 38163, USA
Neuropsychopharmacology 27:587-95. 2002....
Desensitization of Gs-coupled receptor signaling by constitutively active mutants of the human lutropin/choriogonadotropin receptorHiromitsu Shinozaki
Department of Physiology and Biophysics, The University of Iowa, Iowa City, Iowa 52242, USA
J Clin Endocrinol Metab 88:1194-204. 2003....
Research Grants
- Cyclic AMP and the Control of the Meiotic Cell CycleMarco Conti; Fiscal Year: 2007..The studies proposed will further our understanding of the regulation of the specialized meiotic cell cycle as well as the ..
- Role of the EGF Network in OvulationMarco Conti; Fiscal Year: 2007..Finally, a better understanding of the function of EGF-like growth factors will contribute to the understanding of the biology of some tumors of gynecological interest. ..
- GONADAL AND ENDOMETRIAL FUNCTION IN HUMAN REPRODUCTIONRenee Reijo Pera; Fiscal Year: 2007..Advances in the Center are anticipated to lead to new diagnostic and therapeutic modalities for reproductive disorders. ..
- Role of Cyclic Nucleotides in Sperm FunctionMarco Conti; Fiscal Year: 2007..They will also provide the groundwork for validation of targets for pharmacological manipulation of the male gamete, and new diagnostic tools useful to define the male factor. ..
- Role of the EGF Network in OvulationMarco Conti; Fiscal Year: 2007..Finally, a better understanding of the function of EGF-like growth factors will contribute to the understanding of the biology of some tumors of gynecological interest. ..
