title: Androgen receptor phosphorylation: biological context and functional consequences.
abstract: 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 a transcription factor but also as a node that integrates multiple extracellular signals. The AR plays an important role in many diseases, including complete androgen insensitivity syndrome, spinal bulbar muscular atrophy, prostate and breast cancer, etc. 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. Greater understanding of the molecular mechanisms involved in AR action will enable the development of improved therapeutics to treat 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. In this paper, 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.
authors.affiliation: Department of MicrobiologyImmunology, and Cancer BiologyUVA Cancer CenterUniversity of Virginia, PO Box 800734, Charlottesville, Virginia 22908, USA.
authors.forename: Yulia
authors.initials: Y
authors.lastname: Koryakina
authors.affiliation: Department of MicrobiologyImmunology, and Cancer BiologyUVA Cancer CenterUniversity of Virginia, PO Box 800734, Charlottesville, Virginia 22908, USA.
authors.forename: Huy Q
authors.initials: HQ
authors.lastname: Ta
authors.affiliation: Department of MicrobiologyImmunology, and Cancer BiologyUVA Cancer CenterUniversity of Virginia, PO Box 800734, Charlottesville, Virginia 22908, USADepartment of MicrobiologyImmunology, and Cancer BiologyUVA Cancer CenterUniversity of Virginia, PO Box 800734, Charlottesville, Virginia 22908, USA DGG3F@VIRGINIA.EDU.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gioeli
mesh_terms: D000818:Animals; D006801:Humans; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011944:Receptors, Androgen / Q000737:chemistry / Q000378:metabolism*
chemical_list: D011944:Receptors, Androgen; D011494:Protein Kinases
keywords: androgen receptor; cell signaling; gene transcription; growth factor; prostate