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Prostaglandin D2 induces nuclear import of the sex‐determining factor SOX9 via its cAMP‐PKA phosphorylation
Author(s) -
Malki Safia,
Nef Serge,
Notarnicola Cécile,
Thevenet Laurie,
Gasca Stéphan,
Méjean Catherine,
Berta Philippe,
Poulat Francis,
BoizetBonhoure Brigitte
Publication year - 2005
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600660
Subject(s) - biology , nuclear transport , sox9 , phosphorylation , transcription factor , prostaglandin d2 , testis determining factor , microbiology and biotechnology , nuclear protein , importin , nuclear export signal , signal transduction , protein kinase a , nuclear localization sequence , nuclear receptor , cell nucleus , prostaglandin , endocrinology , nucleus , genetics , gene , y chromosome
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 β. 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.