Estrogen receptor-mediated transcription involves the activation of multiple kinase pathways in neuroblastoma cells

Sara Clark, Jennifer Rainville, Xing Zhao, Benita S. Katzenellenbogen, Donald Pfaff, Nandini Vasudevan

Research output: Contribution to journalArticle

Abstract

While many physiological effects of estrogens (E) are due to regulation of gene transcription by liganded estrogen receptors (ERs), several effects are also mediated, at least in part, by rapid non-genomic actions of E. Though the relative importance of rapid versus genomic effects in the central nervous system is controversial, we showed previously that membrane-limited effects of E, initiated by an estradiol bovine serum albumin conjugate (E2-BSA), could potentiate transcriptional effects of 17β-estradiol from an estrogen response element (ERE)-reporter in neuroblastoma cells. Here, using specific inhibitors and activators in a pharmacological approach, we show that activation of phosphatidylinositol-3-phosphate kinase (PI3K) and mitogen activated protein kinase (MAPK) pathways, dependent on a Gαq coupled receptor signaling are important in this transcriptional potentiation. We further demonstrate, using ERα phospho-deficient mutants, that E2-BSA mediated phosphorylation of ERα is one mechanism to potentiate transcription from an ERE reporter construct. This study provides a possible mechanism by which signaling from the membrane is coupled to transcription in the nucleus, providing an integrated view of hormone signaling in the brain.

Original languageEnglish (US)
Pages (from-to)45-53
Number of pages9
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume139
DOIs
StatePublished - Jan 1 2014

Keywords

  • Estrogen receptor phosphorylation
  • G-protein coupled receptor
  • Kinases
  • Signaling
  • Transcription

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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