Androgen receptor phosphorylation: biological context and functional consequences.
Androgen receptor phosphorylation: biological context and functional consequences.
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DOI：
10.1530/erc-13-0472
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发表时间：
2014-08
影响因子：
3.9
通讯作者：
Gioeli D
中科院分区：
文献类型：
--
作者：
Koryakina Y;Ta HQ;Gioeli D
雄激素受体（AR）是一种配体调节的转录因子，属于核受体家族。除了类固醇的调控外，AR还受信号转导途径产生的翻译后修饰的调控。因此，AR不仅具有转录因子的功能，还具有整合多种细胞外信号的节点功能。AR在疾病中的重要性不能被低估，因为它在许多疾病中发挥作用，从完全雄激素不敏感综合征到脊髓球肌萎缩，再到前列腺癌和乳腺癌。在前列腺癌的情况下，依赖于AR信号已被用于治疗干预几十年。然而，由于AR信号的恢复，这些疗法的有效性在晚期疾病中受到限制。充分了解AR作用的分子机制将促进未来治疗广泛AR依赖性疾病的发展。AR通过翻译后对丝氨酸、苏氨酸和酪氨酸残基的修饰受到多种激酶的调控。在这里，我们回顾了AR磷酸化位点，负责这些磷酸化的激酶，以及这些磷酸化的生物学背景和功能后果。最后，讨论了临床样品中已知的AR磷酸化状态。
The androgen receptor (AR) is a ligand-regulated transcription factor that belongs to the family of nuclear receptors. In addition to regulation by steroid, the AR is also regulated by post-translational modifications generated by signal transduction pathways. Thus, the AR functions not only as transcription factor, but also as a node that integrates multiple extracellular signals. The importance of the AR in disease cannot be understated as it plays a role in many diseases ranging from complete androgen insensitivity syndrome to spinal bulbar muscular atrophy to prostate and breast cancer. In the case of prostate cancer, dependence on AR signaling has been exploited for therapeutic intervention for decades. However, the effectiveness of these therapies is limited in advanced disease due to restoration of AR signaling. Fully understanding the molecular mechanisms of AR action will enable the development of future therapeutics for the wide range of AR dependent diseases. The AR is subject to regulation by a number of kinases through post-translational modifications on serine, threonine and tyrosine residues. Here we review the AR phosphorylation sites, the kinases responsible for these phosphorylations, as well as the biological context and the functional consequences of these phosphorylations. Finally, what is known about the state of AR phosphorylation in clinical samples is discussed.