Regulation of estrogen rapid signaling through arginine methylation by PRMT1

Mol Cell. 2008 Jul 25;31(2):212-21. doi: 10.1016/j.molcel.2008.05.025.


Evidence is emerging that estrogen receptor alpha (ERalpha) is central to the rapid transduction of estrogen signaling to the downstream kinase cascades; however, the mechanisms underlying this nongenomic function are not fully understood. Here we report a paradigm of ERalpha regulation through arginine methylation by PRMT1, which transiently methylates arginine 260 within the ERalpha DNA-binding domain. This methylation event is required for mediating the extranuclear function of the receptor by triggering its interaction with the p85 subunit of PI3K and Src. Furthermore, we find that the focal adhesion kinase (FAK), a Src substrate involved in the migration process, is also recruited in this complex. Our data indicate that the methylation of ERalpha is a physiological process occurring in the cytoplasm of normal and malignant epithelial breast cells and that ERalpha is hypermethylated in a subset of breast cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginine / metabolism*
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / pathology
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cytoplasm / drug effects
  • Cytoplasm / metabolism
  • Enzyme Activation / drug effects
  • Estradiol / pharmacology
  • Estrogen Receptor alpha / metabolism
  • Estrogens / pharmacology*
  • Genome, Human / genetics
  • Humans
  • Methylation / drug effects
  • Mice
  • Models, Biological
  • NIH 3T3 Cells
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein-Arginine N-Methyltransferases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins pp60(c-src) / metabolism
  • Receptor Cross-Talk / drug effects
  • Repressor Proteins / metabolism*
  • Signal Transduction / drug effects*
  • Substrate Specificity / drug effects


  • Estrogen Receptor alpha
  • Estrogens
  • Repressor Proteins
  • Estradiol
  • Arginine
  • PRMT1 protein, human
  • Protein-Arginine N-Methyltransferases
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins pp60(c-src)
  • Proto-Oncogene Proteins c-akt