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

Malki, Safia
Notarnicola, Cecile
Gasca, Stephan
Mejean, Catherine
Berta, Philippe
Poulat, Francis
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Published in EMBO Journal. 2005, vol. 24, no. 10, p. 1798-1809
Abstract 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.
Keywords AnimalsCell Nucleus/ metabolismCells, CulturedCyclic AMP/ metabolismCyclic AMP-Dependent Protein Kinases/ metabolismFemaleHigh Mobility Group Proteins/ metabolismMaleMiceOrgan Culture TechniquesOvary/embryology/enzymology/metabolismPhosphorylationProstaglandin D2/ metabolismProtein Transport/physiologySOX9 Transcription FactorTestis/embryology/enzymology/metabolismTranscription Factors/ metabolism
PMID: 15889150
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MALKI, Safia et al. Prostaglandin D2 induces nuclear import of the sex-determining factor SOX9 via its cAMP-PKA phosphorylation. In: EMBO Journal, 2005, vol. 24, n° 10, p. 1798-1809. https://archive-ouverte.unige.ch/unige:8880

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Deposited on : 2010-07-12

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