Prostaglandin D2 induces nuclear import of the sex-determining factor SOX9 via its cAMP-PKA phosphorylation

Article Article scientifique Article Prostaglandin D2 induces nuclear import of the sex-determining factor SOX9 via its cAMP-PKA phosphorylation eng 2005 author Malki Safia author Nef Serge 0000-0001-5462-0676 29062 author Notarnicola Cecile author Thevenet Laurie 649123 author Gasca Stephan author Mejean Catherine author Berta Philippe author Poulat Francis author Boizet-Bonhoure Brigitte 1798-1809 10.1038/sj.emboj.7600660 15889150 0261-4189 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1142593/pdf/7600660a.pdf During mammalian gonadal development, nuclear import/export of the transcription factor SOX9 is a critical step of the Sry-initiated testis-determining cascade. In this study, we identify a molecular mechanism contributing to the SOX9 nuclear translocation in NT2/D1 cells, which is mediated by the prostaglandin D2 (PGD2) signalling pathway via stimulation of its adenylcyclase-coupled DP1 receptor. We find that activation of cAMP-dependent protein kinase A (PKA) induces phosphorylation of SOX9 on its two S64 and S181 PKA sites, and its nuclear localization by enhancing SOX9 binding to the nucleocytoplasmic transport protein importin beta. Moreover, in embryonic gonads, we detect a male-specific prostaglandin D synthase expression and an active PGD2 signal at the time and place of SOX9 expression. We thus propose a new step in the sex-determining cascade where PGD2 acts as an autocrine factor inducing SOX9 nuclear translocation and subsequent Sertoli cell differentiation. Animals Cell Nucleus/ metabolism Cells, Cultured Cyclic AMP/ metabolism Cyclic AMP-Dependent Protein Kinases/ metabolism Female High Mobility Group Proteins/ metabolism Male Mice Organ Culture Techniques Ovary/embryology/enzymology/metabolism Phosphorylation Prostaglandin D2/ metabolism Protein Transport/physiology SOX9 Transcription Factor Testis/embryology/enzymology/metabolism Transcription Factors/ metabolism Dewey 616 56 Département de médecine 221 false EMBO journal 24 10 6abb97a7-2111-4c1f-a56b-17d55fca5fc6 Article Restricted file1.pdf 562567 application/pdf restrictedAccess Faculté de médecine / Section de médecine clinique / Département de médecine

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Prostaglandin D2 induces nuclear import of the sex-determining factor SOX9 via its cAMP-PKA phosphorylation	EMBO journal			2005	623	0

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Thevenet, Laurie