• Home
  1. Home
  2. Prostaglandin D2 induces nuclear import of the sex-determining factor SOX9 via its cAMP-PKA phosphorylation
Scientific article
English

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

Contributors

Malki, Safia; Nef, Serge; Notarnicola, Cecile; Thevenet, Laurie; Gasca, Stephan; Mejean, Catherine; Berta, Philippe; Poulat, Francis; Boizet-Bonhoure, Brigitte

Published in

EMBO journal, vol. 24, no. 10, p. 1798-1809

Publication date

2005

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

  • 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

UNIGE affiliation entities

Citation (ISO format)

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. doi: 10.1038/sj.emboj.7600660

Main files (1)

Article

Identifiers

Additional URL for this publication

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1142593/pdf/7600660a.pdf

Journal ISSN

0261-4189
631views
0downloads

Technical informations

Creation

12/07/2010 11:58:52

First validation

12/07/2010 11:58:52

Update

14/03/2023 15:51:52

Status update

14/03/2023 15:51:51

Last indexation

29/10/2024 15:53:34
All rights reserved by Archive ouverte UNIGE and the University of Geneva
OpenAIRE Indexed & Validated