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首页> 外文期刊>EMBO Journal >Prostaglandin D2 induces nuclear import of the sex-determining factor SOX9 via its cAMP-PKA phosphorylation
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Prostaglandin D2 induces nuclear import of the sex-determining factor SOX9 via its cAMP-PKA phosphorylation

机译：前列腺素D2诱发核进口的通过cAMP-PKA SOX9性别决定因素磷酸化

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摘要

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.
机译：在哺乳动物的性腺发育,核导入/导出的转录因子SOX9Sry-initiated的关键一步精巢决定级联。识别导致的分子机制SOX9核易位在NT2 / D1细胞,它是由前列腺素介导的D2 (PGD2)通过刺激的信号通路adenylcyclase-coupled DP1受体。cAMP-dependent蛋白激酶的激活(PKA)诱发的SOX9磷酸化两个S64和S181 PKA网站,其核通过增强SOX9绑定到本地化核质运输蛋白质importinβ。男性前列腺素D合酶表达和一个活跃的PGD2信号在时间和地点SOX9的表达式。PGD2充当的性别决定级联自分泌因子诱导SOX9核易位和随后的塞尔托利氏细胞分化。

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