title: Membrane androgen receptor characteristics of human ZIP9 (SLC39A) zinc transporter in prostate cancer cells: Androgen-specific activation and involvement of an inhibitory G protein in zinc and MAP kinase signaling.
abstract: Characteristics of novel human membrane androgen receptor (mAR), ZIP9 (SLC39A9), were investigated in ZIP9-transfected PC-3 cells (PC3-ZIP9). Ligand blot analysis showed plasma membrane [3H]-T binding corresponds to the position of ZIP9 on Western blots which suggests ZIP9 can bind [3H]-T alone, without a protein partner. Progesterone antagonized testosterone actions, blocking increases in zinc, Erk phosphorylation and apoptosis, further evidence that ZIP9 is specifically activated by androgens. Pre-treatment with GTPγS and pertussis toxin decreased plasma membrane [3H]-T binding and blocked testosterone-induced increases in Erk phosphorylation and intracellular zinc, indicating ZIP9 is coupled to an inhibitory G protein (Gi) that mediates both MAP kinase and zinc signaling. Testosterone treatment of nuclei and mitochondria which express ZIP9 decreased their zinc contents, suggesting ZIP9 also regulates free zinc through releasing it from these intracellular organelles. The results show ZIP9 is a specific Gi coupled-mAR mediating testosterone-induced MAP kinase and zinc signaling in PC3-ZIP9 cells.
authors.affiliation: University of Texas Marine Science Institute, 750 Channel View Drive, Port Aransas, TX, 78373, USA. Electronic address: peter.thomas@utexas.edu.
authors.forename: Peter
authors.initials: P
authors.lastname: Thomas
authors.affiliation: University of Texas Marine Science Institute, 750 Channel View Drive, Port Aransas, TX, 78373, USA.
authors.forename: Yefei
authors.initials: Y
authors.lastname: Pang
authors.affiliation: University of Texas Marine Science Institute, 750 Channel View Drive, Port Aransas, TX, 78373, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Dong
mesh_terms: D000728:Androgens / Q000494:pharmacology*; D027682:Cation Transport Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D011374:Progesterone / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011944:Receptors, Androgen / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D013739:Testosterone / Q000494:pharmacology; D014316:Tritium / Q000378:metabolism; D015032:Zinc / Q000378:metabolism*
chemical_list: C410798:AR protein, human; D000728:Androgens; D027682:Cation Transport Proteins; C488584:GPRC6A protein, human; D011944:Receptors, Androgen; D043562:Receptors, G-Protein-Coupled; C543108:Slc39a9 protein, human; D014316:Tritium; D013739:Testosterone; D011374:Progesterone; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D015032:Zinc
keywords: Apoptosis; Inhibitory G protein; MAP kinase; Membrane androgen receptor; PC-3 prostate cancer cells; ZIP9; Zinc signaling; Zinc transporter