Phosphorylation of estrogen receptor alpha, serine residue 305 enhances activity

  title={Phosphorylation of estrogen receptor alpha, serine residue 305 enhances activity},
  author={Robin G. Tharakan and Pierig Lepont and David W. Singleton and Rakesh Kumar and Sohaib A. Khan},
  journal={Molecular and Cellular Endocrinology},
Phosphorylation of human estrogen receptor-beta at serine 105 inhibits breast cancer cell migration and invasion
Phosphorylation of the Mutant K303R Estrogen Receptor α at Serine 305 Impacts Aromatase Inhibitor Sensitivity
It is shown that AI resistance arises through an enhanced cross talk of the insulin-like growth factor receptor-1 (IGF-1R)/insulin receptor substrate (IRS)-1/Akt pathway with ERα, and the serine residue 305 adjacent to the K303R mutation has a key function in mediating this cross talk.
Estrogen Receptor-α Phosphorylation at Serine 305, Nuclear p21-Activated Kinase 1 Expression, and Response to Tamoxifen in Postmenopausal Breast Cancer
The results suggest that patients with tumors expressing Pak1 and pERαser305 in combination are a group in which tamoxifen treatment is insufficient, and the pathway may be of interest as a drug target in breast cancer.
Phosphorylation of the Mutant K303R Estrogen Receptor α at Serine 305 Impacts Aromatase Inhibitor Sensitivity.
The data suggest that the K303/S305 residues of the ER α mutation may be a novel determinant of aromatase inhibitor response in breast cancer, and blockade of S305 ERα phosphorylation represents a new therapeutic strategy to overcome resistance to hormonal therapies in tumors with the ERα mutation.
Crosstalk of TTC5 cofactor and the estrogen receptor in breast cancer
This thesis uncovers TTC5 as a novel regulatory factor of ER function, and identifies effects of TTC5 on cell proliferation, enhancing the understanding of ER signalling.
Clinical significance of estrogen receptor phosphorylation.
The hypothesis that phospho-profiling of ERα in human breast tumors to establish an 'ERα phosphorylation code', may be a more accurate marker of prognosis and/or response to endocrine therapy in human Breast cancer is suggested.
Phosphorylation: a fundamental regulator of steroid receptor action
p21-activated kinases in ErbB2-positive breast cancer
The activation of receptor tyrosine kinases, particularly ErbB2, has been linked to the genesis and progression of breast cancer and signaling through the Ras/Raf-1/Mek/Erk pathway, and the PI3K/Akt pathway, which plays an important role in cell survival.


Phosphorylation of Human Estrogen Receptor α by Protein Kinase A Regulates Dimerization
It is shown that ERα is phosphorylated by protein kinase A (PKA) on serine-236 within the DNA binding domain and that in the absence of ligand ERα forms dimers through interaction between DNA binding domains and that dimerization mediated by the ligand binding domain only occurs upon ligandbinding.
Estradiol-induced Phosphorylation of Serine 118 in the Estrogen Receptor Is Independent of p42/p44 Mitogen-activated Protein Kinase*
The data suggest that a kinase other than p42/p44 MAPK is involved in the estradiol-induced Ser118phosphorylation, and it is proposed that the hormone-induced change in ER conformation exposes Ser118 for phosphorylation by a constitutively active kinase.
Function of estrogen receptor tyrosine 537 in hormone binding, DNA binding, and transactivation.
It is shown that phosphorylation of tyrosine 537 is not required for the hER to bind hormone, or to activate transcription, and an alternate model wherein Y537F mutation favors an "open" pocket conformation, affecting the estrogen binding kinetics and stability of the hormone-bound, transcriptionally active "closed" pocket Conformation is proposed.
pp90rsk1 Regulates Estrogen Receptor-Mediated Transcription through Phosphorylation of Ser-167
The results strongly suggest that pp90rsk1 phosphorylates Ser-167 of the human ER in vivo and that Ser- 167 aids in regulating the transcriptional activity of AF-1 in the ER.
P21-activated kinase 1 regulation of estrogen receptor-alpha activation involves serine 305 activation linked with serine 118 phosphorylation.
It is suggested that Pak1 signaling-dependent activation of ER-S305 leads to an enhanced S118 phosphorylation presumably due to a conformational change, and such structural modifications may participate in the development of tamoxifen resistance.
Estrogen receptor phosphorylation
Activation of the unliganded estrogen receptor by EGF involves the MAP kinase pathway and direct phosphorylation.
It is shown that EGF activates the ER by signaling through the MAPK pathway suggesting that MAPK directly phosphorylates the critical serine 118, and implies that the steroid‐independent activation of a variety of ER mutants, which arise during the malignant progression of breast tumors, may contribute to tamoxifen resistance.
Phosphorylation at serines 104 and 106 by Erk1/2 MAPK is important for estrogen receptor-α activity
Data indicate that the MAPK stimulation of ERα activity involves the phosphorylation not only of S118 but also of S104 and S106, and that MAPK-mediated hyperphosphorylation of ER α at these sites may contribute to resistance to tamoxifen in breast cancer.