Phospho-AR (Tyr535) Antibody - #AF8234

Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription factor activity is modulated by bound coactivator and corepressor proteins like ZBTB7A that recruits NCOR1 and NCOR2 to the androgen response elements/ARE on target genes, negatively regulating androgen receptor signaling and androgen-induced cell proliferation. Transcription activation is also down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3.

Isoform 3 and isoform 4 lack the C-terminal ligand-binding domain and may therefore constitutively activate the transcription of a specific set of genes independently of steroid hormones.

Sumoylated on Lys-388 (major) and Lys-521. Ubiquitinated. Deubiquitinated by USP26. 'Lys-6' and 'Lys-27'-linked polyubiquitination by RNF6 modulates AR transcriptional activity and specificity.

Phosphorylated in prostate cancer cells in response to several growth factors including EGF. Phosphorylation is induced by c-Src kinase (CSK). Tyr-535 is one of the major phosphorylation sites and an increase in phosphorylation and Src kinase activity is associated with prostate cancer progression. Phosphorylation by TNK2 enhances the DNA-binding and transcriptional activity and may be responsible for androgen-independent progression of prostate cancer. Phosphorylation at Ser-83 by CDK9 regulates AR promoter selectivity and cell growth. Phosphorylation by PAK6 leads to AR-mediated transcription inhibition.

Palmitoylated by ZDHHC7 and ZDHHC21. Palmitoylation is required for plasma membrane targeting and for rapid intracellular signaling via ERK and AKT kinases and cAMP generation.

Nucleus. Cytoplasm.
Note: Detected at the promoter of target genes (PubMed:25091737). Predominantly cytoplasmic in unligated form but translocates to the nucleus upon ligand-binding. Can also translocate to the nucleus in unligated form in the presence of RACK1.

Isoform 2 is mainly expressed in heart and skeletal muscle. Isoform 3 is expressed by basal and stromal cells of prostate (at protein level).

Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain. In the presence of bound steroid the ligand-binding domain interacts with the N-terminal modulating domain, and thereby activates AR transcription factor activity. Agonist binding is required for dimerization and binding to target DNA. The transcription factor activity of the complex formed by ligand-activated AR and DNA is modulated by interactions with coactivator and corepressor proteins (PubMed:25091737). Interaction with RANBP9 is mediated by both the N-terminal domain and the DNA-binding domain. Interaction with EFCAB6/DJBP is mediated by the DNA-binding domain.

Belongs to the nuclear hormone receptor family. NR3 subfamily.