title: Splicing potentiation by growth factor signals via estrogen receptor phosphorylation.
abstract: Mitogen-activated protein kinase-mediated growth factor signals are known to augment the ligand-induced transactivation function of nuclear estrogen receptor alpha (ERalpha) through phosphorylation of Ser-118 within the ERalpha N-terminal transactivation (activation function-1) domain. We identified the spliceosome component splicing factor (SF)3a p120 as a coactivator specific for human ERalpha (hERalpha) activation function-1 that physically associated with ERalpha dependent on the phosphorylation state of Ser-118. SF3a p120 potentiated hERalpha-mediated RNA splicing, and notably, the potentiation of RNA splicing by SF3a p120 depended on hER Ser-118 phosphorylation. Thus, our findings suggest a mechanism by which growth factor signaling can regulate gene expression through the modulation of RNA splicing efficiency via phosphorylation of sequence-specific activators, after association between such activators and the spliceosome.
authors.affiliation: Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Masuhiro
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Mezaki
authors.forename: Matomo
authors.initials: M
authors.lastname: Sakari
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Takeyama
authors.forename: Tasuku
authors.initials: T
authors.lastname: Yoshida
authors.forename: Kunio
authors.initials: K
authors.lastname: Inoue
authors.forename: Junn
authors.initials: J
authors.lastname: Yanagisawa
authors.forename: Shigemasa
authors.initials: S
authors.lastname: Hanazawa
authors.forename: Bert W
authors.initials: BW
authors.lastname: O'malley
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Kato
mesh_terms: D000818:Animals; D002460:Cell Line; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010768:Phosphoserine / Q000378:metabolism; D011485:Protein Binding; D012326:RNA Splicing / Q000187:drug effects*; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D017381:Spliceosomes / Q000378:metabolism
chemical_list: D047628:Estrogen Receptor alpha; D006133:Growth Substances; D017413:Ribonucleoprotein, U2 Small Nuclear; C088049:splicing factor 3a; D010768:Phosphoserine; D020928:Mitogen-Activated Protein Kinases