Department of Public Health and Cell Biology Prof. Claudio Sette CURRICULUM VITAE Name: Claudio Sette Date and Place of Birth: November 24th, 1966, Rome, Italy Education: 1985: High School Degree, Instituto Liceo G. Piazzi Morlupo (Rome, Italy) 1992: Doctor cum Laude in Biological Sciences, University of Rome La Sapienza (Rome, Italy) 1998: PhD in Medical Embryology, University of Rome Tor Vergata, (Rome, Italy) Current Position: Associate Professor of Anatomy Department of Public Health and Cell Biology, School of Medicine University of Rome Tor Vergata Via Montpellier 1, 00133, Rome Telefono 39672596260 FAX 39672596268 Email: [email protected] Professional Experience: 2010-to date Associate Member of the European Alternative Splicing Network (EURASNET) 2006-to date Joint appointment as Laboratory Director at the Institute for Experimental Neurosciences, Fondazione Santa Lucia, Rome (Italy) 2002-to date Associate Professor at the Department of Public Health and Cell biology, University of Rome Tor Vergata, (Italy) 2001-2002 Researcher at the Department of Public Health and Cell biology, University of Rome Tor Vergata, (Italy) 1998-2000 Postdoctoral Fellow at the Department of Molecular and Cell Biology, University of California at Berkeley (California, USA) 1995-1998 PhD student in Medical Embryology at the Department of Public Health and Cell biology, University of Rome Tor Vergata (Italy) 1995-1996 1993-1995 1990-1992 Invited Scientist at the INSA, School of Engeneering, Department of Biological Chemistry, INSERM Unit 352 , Lyon, (France). (December 1995- February 1996) Research Fellow at the Department of Obstetrics and Gynecology, Stanford University, California U.S.A. Undergraduate Internship at the Department of Biological Chemistry, University of Rome La Sapienza (Italy). Awards: 1992 1993-1995 1998-2000 Research Fellowship by the Fondazione Cenci-Bolognetti, University of Rome La Sapienza. Dean’s Fellowship by Stanford University (California, USA). Postdoctoral Fellowship by the American-Italian Cancer Foundation. Scientific Experience and Interests The laboratory of Prof. Sette is involved in several aspects of the biology of germ cells, neurons and cancer cells. The major interests are centered around the regulation of the post-transcriptional control of gene expression. Our laboratory aims at studying the regulation of mRNA processing and gene expression by RNA-binding proteins whose activity is modulated by signal transduction pathways, cell differentiation programs or oncogenic transformation. As prototypic RNA binding protein, we have focused the attention on Sam68, which is required for male fertility and brain functions and is up-regulated in several cancers, including prostate, renal and testicular carcinomas. The laboratory is also focused in developing biological drugs to interfere with the function of proteins in pathological situations. Grants obtained in the last 5 years: 2002-2008: “Identification and characterization of small molecole inhibitors of the MyD88inflammatory pathway”; EURO 60000/year, funded by SIGMA-TAU s.p.a Pharmaceutical Industry and TECNOGEN Biotechnology. 2004-2006: “Role of the interaction between Src kinase and the RNA-binding protein Sam68 in human prostate carcinoma” ; EURO 120000, funded by AIRC (Italian Association for Cancer Research). 2004-2005: “Modulation of gene expression at the translational level by androgens in prostate cancer cells”. EURO 53000; funded by the Italian Ministry of Education (PRIN 2004). 2004-2006: “Translational control of the molecular mechanisms of the onset of embryogenesis”. EURO 131500, funded by Telethon 2005-2008: “Centrosome overduplication in human testicular seminomas”. $223000, funded by the Lance Armstrong Foundation (U.S.A.). 2006-2007: “Post-transcriptional regulation by steroids and growth factors in prostate cancer cells”. EURO 40000; funded by the Italian Ministry of Education (PRIN 2006). 2007: “Role of Toll-like receptors and MyD88 in multiple sclerosis”. EURO 25000, funded by Italian Foundation for Multiple Sclerosis (FISM). 2007-2009: “Role of the RNA-binding protein Sam68 in human prostate carcinoma”. EURO 140000; funded by funded by AIRC (Italian Association for Cancer Research). 2008-2010: “Role of the RNA-binding protein Sam68 in human prostate carcinoma”. UK £ 97000; funded by AICR (Association for International Cancer Research). 2009-2012: “Regulation of the alternative splicing of SMN2 by Sam68 and its implication in Spinal Muscular Atrophy”. EURO 198000; funded by Telethon. 2010-2013: “Role of the multifunctional RNA binding protein Sam68 in human prostate cancer”. EURO 225000; funded by AIRC (Italian Association for Cancer Research). 2010-2013: “Role of Sam68 in the regulation of SMN2 alternative splicing in SMA cells”. U.S $ 219000; funded by the Muscular Dystrophy Association (U.S.A.) 2011-2014: “Role of the RNA-binding protein Sam68 in human prostate carcinoma”. UK £ 135000; funded by AICR (Association for International Cancer Research). IMPEGNO DIDATTICO-FORMATIVO NELL’AMBITO DEL DOTTORATO A) Tutor durante l’attività sperimentale, nell’ultimo anno accademico e/o precedenti, dei seguenti dottorandi: Manuela Cappellari (2010-2012) Sara Calabretta (2010-2012) Chiara Naro (2011-2012) Maria Blaire Bustamante (2011-2012) Ilaria Passacantilli (2012) B) Tutor durante la preparazione della tesi di dottorato, nell’ultimo anno accademico e/o precedenti, dei seguenti dottorandi: Valeria Messina (2011) Simona Pedrotti (2011) Federica Barbagallo (2010) Laura Adesso (2010) C) Attività seminariale, nell’ultimo anno accademico e/o precedenti: Titolo seminario: 1) Regolazione del differenziamento delle cellule embrionali staminali mediante lo splicing alternativo di un fattore di trascrizione (2012) 2) Ruolo dello splicing alternative nelle patologie umane e nuovi strumenti per la sua modulazione in vivo (2011) List of peer-reviewed articles 1. Capurso G, Sette C, Delle Fave G. (2012) The role of SRC family kinases in neuroendocrine tumors. Gastroenterology. 142(4):e19. 2. Pedrotti S, Busà R, Compagnucci C, Sette C. (2012) The RNA recognition motif protein RBM11 is a novel tissue-specific splicing regulator. Nucleic Acids Res. 40:1021-32. 3. Capurso G, Di Florio A, Sette C, Delle Fave G. (2012) Signalling Pathways Passing Src in Pancreatic Endocrine Tumours: Relevance for Possible Combined Targeted Therapies. Neuroendocrinology. Mar 21. [Epub ahead of print] 4. De Cola A, Bongiorno-Borbone L, Bianchi E, Barcaroli D, Carletti E, Knight RA, Di Ilio C, Melino G, Sette C, De Laurenzi V. (2012) FLASH is essential during early embryogenesis and cooperates with p73 to regulate histone gene transcription. Oncogene. 31:573-82. 5. Di Florio A, Adesso L, Pedrotti S, Capurso G, Pilozzi E, Corbo V, Scarpa A, Geremia R, Delle Fave G, Sette C. (2011) Src kinase activity coordinates cell adhesion and spreading with activation of mammalian target of rapamycin in pancreatic endocrine tumour cells. Endocr Relat Cancer. 18:541-54. 6. Bielli P, Busà R, Paronetto MP, Sette C. (2011) The RNA binding protein Sam68 is a multifunctional player in human cancer. Endocr Relat Cancer. 18(4):R91R102. 7. Chen J, Melton C, Suh N, Oh JS, Horner K, Xie F, Sette C, Blelloch R, Conti M. (2011) Genome-wide analysis of translation reveals a critical role for deleted in azoospermia-like (Dazl) at the oocyte-to-zygote transition. Genes Dev. 2011 25:755-66. 8. Paronetto MP, Messina V, Barchi M, Geremia R, Richard S, Sette C. (2011) Sam68 marks the transcriptionally active stages of spermatogenesis and modulates alternative splicing in male germ cells. Nucleic Acids Res. 39(12):4961-74. 9. Loiarro M, Campo S, Arseni B, Rossi S, D'Alessio V, De Santis R, Sette C, Ruggiero V. (2011) Anti-proliferative effect of a triazole derivative (ST1959) on LNCaP human prostate cancer cells through down-regulation of cyclin and androgen receptor expression. Prostate. 71:32-41. 10. Sette C. (2010) Post-translational regulation of star proteins and effects on their biological functions. Adv Exp Med Biol. 693:54-66. 11. Bianchi E, Barbagallo F, Valeri C, Geremia R, Palustri A, De Felici M, Sette C. (2010) Ablation of the Sam68 gene impairs fertilità and gonadotropin-dependent follicle development. Hum. Mol. Genet. 19:4886-94. 12. Valacca C, Bonomi S, Buratti E, Pedrotti S, Baralle FE, Sette C, Ghigna C, Biamonti G. (2010) Sam68 regulates EMT through alternative splicing-activated nonsense-mediated mRNA decay of the SF2/ASF proto-oncogene. J Cell Biol. 191:87-99. 13. Pedrotti S, Sette C. (2010) Spinal Muscular Atrophy: a novel player joins the battle for SMN2 exon 7 splicing. Cell Cycle. (19):3874-9. 14. Capolunghi F, Rosado MM, Cascioli S, Girolami E, Bordasco S, Vivarelli M, Ruggiero B, Cortis E, Insalaco A, Fantò N, Gallo G, Nucera E, Loiarro M, Sette C, De Santis R, Carsetti R, Ruggiero V. (2010) Pharmacological inhibition of TLR9 activation blocks autoantibody production in human B cells from SLE patients. Rheumatology. 49:2281-9. 15. Busà R, Sette C. (2010) An emerging role for nuclear RNA-mediated responses to genotoxic stress. RNA Biology. 17; 7(4). 16. Muciaccia B, Sette C, Paronetto MP, Barchi M, Pensini S, D'Agostino A, Gandini L, Geremia R, Stefanini M, Rossi P. (2010) Expression of a truncated form of KIT tyrosine kinase in human spermatozoa correlates with sperm DNA integrity. Hum Reprod. 25:2188-202. 17. Messina V, Di Sauro A, Pedrotti S, Adesso L, Latina A, Geremia R, Rossi P, Sette C. (2010) Different Contribution of the MTOR and MNK Pathways to the Regulation of mRNA Translation in Meiotic and Post-Meiotic Mouse Male Germ Cells. Biol Reprod. 83:607-15. 18. Galli R, Starace D, Busà R, Angelini DF, Paone A, De Cesaris P, Filippini A, Sette C, Battistini L, Ziparo E, Riccioli A. (2010) TLR stimulation of prostate tumor cells induces chemokine-mediated recruitment of specific immune cell types. J Immunol. 184:6658-69. 19. Olshavsky NA, Comstock CE, Schiewer MJ, Augello MA, Hyslop T, Sette C, Zhang J, Parysek LM, Knudsen KE. (2010) Identification of ASF/SF2 as a critical, allele-specific effector of the cyclin D1b oncogene. Cancer Res. 70: 3975-84. 20. Bianchi E, Geremia R, Sette C. (2010) Expression of stemness markers in mouse parthenogenetic-diploid blastocysts is influenced by slight variation of activation protocol adopted. In Vitro Cell Dev Biol Anim. 2010 Apr 8. [Epub ahead of print]. 21. Loiarro M, Ruggiero V, Sette C. (2010) Targeting TLR/IL-1R signalling in human diseases. Mediators Inflamm. 2010:674363. 22. Pedrotti S, Bielli P, Paronetto MP, Ciccosanti F, Fimia GM, Stamm S, Manley JL, Sette C. (2010) The splicing regulator Sam68 binds to a novel exonic splicing silencer and functions in SMN2 alternative splicing in spinal muscular atrophy. EMBO J. 29:1235-47. 23. Busà R, Geremia R, Sette C. (2010) Genotoxic stress causes the accumulation of the splicing regulator Sam68 in nuclear foci of transcriptionally active chromatin. Nucleic Acids Res. 38: 3005-18. 24. Paronetto MP, Cappellari M, Busà R, Pedrotti S, Vitali R, Comstock C, Hyslop T, Knudsen KE, Sette C. (2010) Alternative splicing of the cyclin D1 protooncogene is regulated by the RNA-binding protein Sam68. Cancer Res. 70:22939. 25. Sette C, Messina V, Paronetto MP. (2010) Sam68: A New STAR in the Male Fertility Firmament. J Androl. 31:66-74. 26. Paronetto MP, Sette C. (2010) Role of RNA-binding proteins in mammalian spermatogenesis. Int J Androl. 33: 2-12. 27. Brignatz C, Paronetto MP, Opi S, Cappellari M, Audebert S, Feuillet V, Bismuth G, Roche S, Arold ST, Sette C, Collette Y. (2009) Alternative splicing modulates auto-inhibition and SH3 accessibility in the Src kinase Fyn. Mol Cell Biol. 29(24):6438-48. 28. Loiarro M, Gallo G, Fantò N, De Santis R, Carminati P, Ruggiero V, Sette C. (2009) Identification of critical residues of the MyD88 death domain involved in the recruitment of downstream kinases. J Biol Chem. 284:28093-103. 29. Paronetto MP, Messina V, Bianchi E, Barchi M, Vogel G, Moretti C, Palombi F, Stefanini M, Geremia R, Richard S, Sette C. (2009) Sam68 regulates translation of target mRNAs in male germ cells, necessary for mouse spermatogenesis. J Cell Biol. 185:235-49. 30. Barbagallo F, Paronetto MP, Franco R, Chieffi P, Dolci S, Fry AM, Geremia R, Sette C. (2009) Increased expression and nuclear localization of the centrosomal kinase Nek2 in human testicular seminomas. J Pathol. 217:431-41. 31. Bianchini A, Loiarro M, Bielli P, Busà R, Paronetto MP, Loreni F, Geremia R, Sette C. (2008) Phosphorylation of eIF4E by MNKs supports protein synthesis, cell cycle progression and proliferation in prostate cancer cells. Carcinogenesis. 29:2279-88. 32. Ehrmann I, Dalgliesh C, Tsaousi A, Paronetto MP, Heinrich B, Kist R, Cairns P, Li W, Mueller C, Jackson M, Peters H, Nayernia K, Saunders P, Mitchell M, Stamm S, Sette C, Elliott DJ. (2008) Haploinsufficiency of the germ cell-specific nuclear RNA binding protein hnRNP G-T prevents functional spermatogenesis in the mouse. Hum Mol Genet. 17:2803-18. 33. Paronetto MP, Bianchi E, Geremia R, Sette C. (2008) Dynamic expression of the RNA-binding protein Sam68 during mouse pre-implantation development. Gene Expr. Patterns, 8:311-22 . 34. Fedele M, Franco R, Salvatore G, Paronetto MP, Barbagallo F, Pero R, Chiaritoti L, Sette C, Tramontano D, Chieffi G, Fusco A, Chieffi P. (2008) PATZ1 gene has a critical role in the spermatogenesis and testicular tumours. J. of Pathology, 215:39-47. 35. Iwasaki T, Koretomo Y, Fukuda T, Paronetto MP, Sette C, Fukami Y, Sato K. (2008) Expression, phosphorylation, and mRNA-binding of heterogeneous nuclear ribonucleoprotein K in Xenopus oocytes, eggs, and early embryos. Dev Growth Differ. 50:23-40. 36. Paronetto MP, Achsel T, Massiello A, Chalfant CE, and Sette C. (2007) The RNA-binding protein Sam68 modulates the alternative splicing of Bcl-x. J Cell Biol. 176:929-39. 37. Godmann M, Auger V, Ferraroni-Aguiar V, Di Sauro A, Sette C, Behr R, Kimmins S. (2007) Dynamic regulation of histone H3 methylation at lysine 4 in mammalian spermatogenesis. Biol Reprod. 77:754-764. 38. Busà R, Paronetto MP, Farini D, Pierantozzi E, Botti F, Angelini DF, Attisani F, Vespasiani G, and Sette C. (2007) The RNA-binding protein Sam68 contributes to proliferation and survival of human prostate cancer cells. Oncogene, 26:437282. 39. Sette C. (2007) Rational design of MyD88 inhibitors--new pathways to inflammatory control: an interview with Dr. Claudio Sette by Helene F. Rosenberg. J Leukoc Biol. 82:811-812. 40. Loiarro M, Capolunghi F, Gallo G, Fantò N, De Santis R, Carminati P, Carsetti R, Ruggiero V, and Sette C. (2007) Inhibition of MyD88 dimerization and of recruitment of IRAK1 and IRAK4 by a novel peptidomimetic compound. J Leukoc. Biol. 82:801-10. 41. Di Florio A, Capurso G, Milione M, Panzuto F, Geremia R, delle Fave GF, and Sette C. (2007) Src-related kinase activity regulates adhesion, spreading and migration of pancreatic endocrine tumour cells. Endocrine-related Cancer. 14:111-24. 42. Paronetto MP, Zalfa F, Botti F, Geremia R, Bagni C, and Sette C. (2006) The nuclear RNA-binding protein Sam68 translocates to the cytoplasm and associates with the polysomes in mouse spermatocytes. Mol Biol Cell. 17:14-24. 43. Vicini E, Loiarro M, Di Agostino S, Corallini S, Capolunghi F, Carsetti R, Chieffi P, Geremia R, Stefanini M, and Sette C. (2006) 17-β-estradiol elicits genomic and non-genomic responses in mouse male germ cells. J. Cell Physiol. 206(1):238-45. 44. Loiarro M, Sette C, Gallo G, Fantò N, Mastroianni D, Carminati P, and Ruggiero V. (2005) Peptide-mediated interference of TIR domain dimerization in MyD88 inhibits IL-1-dependent activation of NF-B. J. Biol. Chem. 280: 15809-15814. 45. Capurso G, Crnogorac-Jurcevic T, Milione M, Panzuto F, Campanini N, Dowen SE, Di Florio A, Sette C, Bordi C, Lemoine NR, Delle Fave G. (2005) Peanutlike 1 (septin 5) gene expression in normal and neoplastic human endocrine pancreas. Neuroendocrinology. 81:311-21. 46. Paronetto MP, Giorda E, Carsetti R, Rossi P, Geremia R, and Sette C. (2004) Functional interaction between p90(Rsk2) and Emi1 contributes to the metaphase arrest of mouse oocytes. EMBO J. 23: 4649-4659. 47. Di Agostino S, Botti F, Di Carlo A, Sette C, and Geremia R. (2004) Meiotic progression of isolated mouse spermatocytes under simulated microgravity. Reproduction. 128:25-32. 48. Venables JP, Dalgliesh G, Paronetto MP, Skitt L, Thornton JK, Saunders PT, Sette C, Jones KT, and Elliott DJ. (2004) SIAH1 targets the alternative splicing factor T-STAR for degradation by the proteasome. Hum. Mol. Genet. 13:15251532. 49. Sammarco I, Capurso G, Coppola L, Bonifazi AP, Cassetta S, Delle Fave G, Carrara A, Grassi GB, Rossi P, Sette C, and Geremia R. (2004) Expression of the proto-oncogene c-KIT in normal and tumor tissues from colorectal carcinoma patients. Int J Colorectal Dis. 19 :545-553. 50. Rossi P, Dolci S, Sette C, Capolunghi F, Pellegrini M, Loiarro M, Di Agostino S, Paronetto MP, Grimaldi P, Merico D, Martegani E, and Geremia R. (2004) Analysis of the gene expression profile of male meiotic germ cells. Gene Expr. Patterns 4:267-281. 51. Paronetto MP, Farini D, Sammarco I, Maturo G, Vespasiani G, Geremia R, Rossi P, and Sette C. (2004) Expression of a truncated form of the c-Kit tyrosine kinase receptor and activation of Src kinase in human prostatic cancer. Am. J. of Pathology. 164: 1243-1251. 52. Di Agostino S., Fedele M., Chieffi P., Fusco A., Rossi P., Geremia R., and Sette C. (2004) Phosphorylation of High Mobility Group Protein A2 by Nek2 Kinase During the First Meiotic Division in mouse spermatocytes. Mol Biol Cell. 15: 1224-1232. 53. Sato K-I, Sette C, Kurokawa M, Paronetto MP, Iwasaki T, Fukami Y, and Fissore RA. (2004) Fertilizome project: Proteomics of Fertilization signaling, the biological bridge between gametogenesis and embryogenesis. Current Proteomics, 1:231-246. 54. Paronetto MP, Venables JP, Elliott DJ, Geremia R, Rossi P, Sette C. (2003) Tr-kit promotes the formation of a multimolecular complex composed by Fyn, PLCgamma1 and Sam68. Oncogene. 22:8707-8715. 55. Naro F, De Arcangelis V, Sette C, Ambrosio C, Komati H, Molinaro M, Adamo S, Nemoz G. (2003) A bimodal modulation of the cAMP pathway is involved in the control of myogenic differentiation in l6 cells. J Biol Chem. 278:49308-49315. 56. Rossi P, Dolci S, Sette C, Geremia R. (2003) Molecular mechanisms utilized by alternative c-kit gene products in the control of spermatogonial proliferation and sperm-mediated egg activation. Andrologia. 35:71-78. 57. Sette, C., Paronetto, M.P., Barchi, M., Bevilacqua, A., Geremia, R., and Rossi, P. (2002) Tr-kit-induced resumption of the cell cycle in mouse eggs requires activation of a Src-like kinase. EMBO J. 21:5386-5395. 58. Diaz, O., Berquand, A., Dubois, M., Di Agostino, S., Sette, C., Lagarde, M., Nemoz, G., and Prigent, A-F. (2002) The mechanism of docosohexcaenoic acidinduced phospholipase D activation in human lymphocytes involves exclusion of the enzyme from lipid rafts. J. Biol. Chem., 277:39368-78. 59. Di Agostino S., Rossi P:, Geremia R., and Sette C. (2002) The MAPK pathway triggers Nek2 activation during chromosome condensation in mouse spermatocytes. Development, 129, 1715-1727. 60. Kunzler M., Trueheart J., Sette C., Hurt E., and Thorner J. (2001) Mutations in the yrb1 gene encoding yeast ran-binding-protein-1 that impair nucleocytoplasmic transport and suppress yeast mating defects. Genetics. 157:1089-105. 61. Sette C., Inouye C.J., Stroschein S.L., Iaquinta P.J., and Thorner J. (2000) Mutational analysis of STE5: evidence that activation occurs by relief of intramolecular inhibition. Molecular Biology of the Cell. 11:4033-49. 62. Sette C., Dolci S., Geremia R., and Rossi P. (2000) Role of c-kit in the establishment, maintainance and function of germ cells. Int. J. Dev. Biol. 44:599608. 63. Rossi P., Sette C., Dolci S., Geremia R. (2000) Role of c-kit in mammalian spermatogenesis. J. Endocrinol. Invest. 23:609-15. 64. Grange, M., Sette, C., Prigent, A.F., & Nemoz, G. (2000) Activation of PDE4D3 by direct binding of phosphatidic acid. J. Biol. Chem., 275:33379-87. 65. Naro F., Sette, C., Vicini, E., Grange, M., Conti, M., Lagarde, M., Molinaro, M., Adamo, S., Nemoz, G. (1999) Involvement of type 4 cyclic AMPphosphodiesterase in the myogenic differentiation of L6 cells. Molecular Biology of the Cell, 10, 4355-4367. 66. Sette, C., Barchi, M., Bianchini, A., Conti, M., Rossi, P., and Geremia, R. (1999) Activation of the mitogen activated protein kinase ERK1 during the G2/M progression of mouse pachitene spermatocytes. J. Biol. Chem., 274, 3357133579. 67. Grange M, Sette C, Prigent AF, Lagarde M, Nemoz G. (1999) Regulation of cAMP-phosphodiesterases by phosphatidic acid binding. Lipids. 34, Suppl:S83. 68. Naro F, Vicini E, Sette C, Grange M, Prigent AF, Curci R, Lagarde M, Nemoz G, Adamo S. (1999) Phosphatidic acid-dependent activation of adenosine-3',5'cyclic-monophosphate-phosphodiesterase is necessary for Arg-vasopressin induction of myogenesis. Lipids. 34, Suppl:S81-2. 69. Giordano D, Giorgi M, Sette C, Biagioni S, Augusti-Tocco G (1999) cAMPdependent induction of PDE5 expression in murine neuroblastoma cell differentiation. FEBS Lett 446:218-22. 70. Sette, C., Bevilacqua, A., Geremia, R., and Rossi, P. (1998) Involvement of phospholipase Cg1 in mouse egg activation induced by a truncated form of the ckit tyrosine kinase present in spermatozoa. J. Cell Biol 142, 1063-1074. 71. Iona, S., Cuomo, M., Bushnik, T., Naro, F., Sette, C., Hess, M., Shelton, E.R., and Conti, M. (1998) Characyerization of the rolipram-sensitive, cAMP-specific phosphodiesterases: identification and differential expression of immunologically distincts forms in the rat brain. Molecular Pharmacology 53, 23-32. 72. El Bawab, S., Macovschi, O., Sette, C., Conti, M., Lagarde, M., Nemoz, G., and Prigent, A-F. (1997) Selective stimulation of cAMP-specific phosphodiesterase (PDE4A5) isoform by phosphatidic acid molecular species endogenously formed in rat thymocytes. European Journal of Biochemistry, 247, 1151-1157. 73. Sette, C., Bevilacqua, A., Bianchini, A., Mangia, F., Geremia, R., and Rossi, P. (1997) Parthenogenetic activation of mouse eggs by microinjection of a truncated c-kit tyrosine kinase present in spermatozoa. Development, 124, 2267-2272. 74. Nemoz, G., Sette, C., and Conti, M. (1997) Selective activation of rolipramsensitive, cAMP-specific phosphodiesterase isoforms by phosphatidic acid. Molecular Pharmacology, 51, 242-249. 75. Sette, C., and Conti, M. (1996) Phosphorylation and activation of a cAMPspecific phosphodiesterase by the cAMP-dependent protein kinase: involvement of serine 54 in the activation. J. Biol. Chem., 271, 16256-16534. 76. Nemoz, G., Zhang, R., Sette, C., and Conti, M. (1996) Identification of cyclic AMP-phosphodiesterase variants expressed from the PDE4D gene in human peripheral mononuclear cells. FEBS Letters, 384, 97-102. 77. Albanesi, C., Geremia, R., Giorgio, M., Dolci, S., Sette, C., and Rossi, P. (1996) A cell- and developmental stage-specific promoter drives the expression of a truncated c-kit protein during mouse spermatid elongation. Development, 122, 1291-1302. 78. Alvarez R., Sette, C., Yang, D., Eglen, R.M., Wilhelm, R., Shelton, E.R., and Conti, M. (1995) Activation and selective inhibition of a cyclic AMP-specific phosphodiesterase (PDE4D3). Molecular Pharmacology, 48,616-622. 79. Nemoz, G. Sette, C., Hess, M., Muca, C., Vallar, L., and Conti, M. (1995) Activation of cyclic nucleotide phosphodiesterases in FRTL-5 thyroid cellsexpressing a constitutively active Gs. Molecular Endocrinology, 9,12791287. 80. Conti, M., Nemoz, G., Sette, C., and Vicini, E. (1995) Recent progress inunderstanding the hormonal regulation of phosphodiesterases. Endocrine Reviews, 16, 370-389. 81. Sette, C., Vicini, E., and Conti, M. (1994) The ratPDE3/IVd gene codes for multiple proteins differentially activated by cAMP-dependent protein kinase. J. Biol. Chem., 269, 18271-18274. 82. Sette, C., Iona, S., and Conti, M. (1994) The short-term activation of arolipramsensitive, cAMP-specific phosphodiesterase by TSH in thyroid FRTL-5 cells is mediated by a cAMP-dependent phosphorylation. J. Biol. Chem., 269, 9245-9252. 83. Sette, C., Vicini, E., and Conti, M. (1994) Modulation of cellular responses by hormones: role of cAMP-specific, rolipram-sensitive phosphodiesterase. Molecular and Cellular Endocrinology, 100, 75-79.