Phospho-Estrogen Receptor α (Ser167) Antibody [D20F17]

Application: Reactivity: Human

Usage Information

Dilution
WB1:1000 IF1:800

Application
WB, IF

Reactivity
Human

Source
Rabbit Monoclonal Antibody

Storage Buffer
PBS, pH 7.2+50% Glycerol+0.05% BSA+0.01% NaN3

Storage (from the date of receipt)
-20°C (avoid freeze-thaw cycles), 2 years

Predicted MW
66 kDa

Datasheet & SDS

Biological Description

Specificity
Phospho-Estrogen Receptor α (Ser167) Antibody [D20F17] detects endogenous levels of total Estrogen Receptor α protein only when it is phosphorylated at Ser167.

Clone
D20F17

Synonym(s)
DKFZp686N23123, E2 receptor alpha, ER, ER-alpha, Era, ESR, ESR1, ESRA, Estradiol receptor, estrogen receptor alpha E1-N2-E2-1-2, ESTRR, NR3A1, Nuclear receptor subfamily 3 group A member 1, oestrogen receptor alpha

Background
Phospho–estrogen receptor α (Ser167) represents a ligand- and growth factor–regulated form of ERα, a steroid receptor family transcription factor that integrates estrogen signaling with multiple kinase cascades through its modular DNA-binding domain, ligand-binding domain, and N‑terminal AF‑1 activation region that contains Ser167 within a cluster of regulatory serines. The AF‑1 domain harbors Ser104, Ser106, Ser118, and Ser167, and phosphorylation at these residues modulates ERα transcriptional output by altering receptor conformation, chromatin association, and coactivator recruitment, with Ser167 acting as a key node for cross-talk between estrogen and kinase pathways such as mTOR/S6K1, MAPK/p90RSK, Akt, and IKKϵ. Kinases activated downstream of growth factor receptors and oncogenic signaling, including S6K1, RSK, Akt, and IKKϵ, directly phosphorylate Ser167, which enhances ERα-dependent transcriptional activity and supports estrogen-responsive gene expression even under conditions of low ligand, thereby promoting cell-cycle progression and proliferation in ERα-positive tumor cells. Site-specific modulation of Ser167 phosphorylation shapes the temporal pattern of ERα and coactivator complex recruitment to estrogen-responsive promoters and influences the spectrum of target genes that control growth, survival, migration, and invasion, so that Ser167 acts not only as a binary activation mark but also as a determinant of transcriptional programs linked to tumor behavior and therapeutic response. Phosphorylation of Ser167 correlates with activation of upstream MAPK and S6K1 pathways and with increased nuclear accumulation of phospho-ERα, highlighting its position as a downstream readout of mitogenic kinase activity and as a convergence point where growth factor and estrogen signals cooperate to maintain ERα-driven transcription. Clinical analyses of ERα-positive breast cancers show that detection of ERα phosphorylated on Ser167 associates with response to endocrine therapy and with improved post-relapse survival in metastatic settings, indicating that this modification marks tumors that retain functional ER signaling capacity even in the presence of endocrine agents. At the same time, persistent or kinase-driven Ser167 phosphorylation contributes to ligand-independent ERα activation and to resistance mechanisms against tamoxifen and other endocrine treatments, as growth factor–dependent phosphorylation sustains ERα target gene transcription despite receptor antagonism and links phospho-Ser167 status to poor prognosis in subsets of hormone-dependent malignancies, including breast and endometrial cancers.

Background

Phospho–estrogen receptor α (Ser167) represents a ligand- and growth factor–regulated form of ERα, a steroid receptor family transcription factor that integrates estrogen signaling with multiple kinase cascades through its modular DNA-binding domain, ligand-binding domain, and N‑terminal AF‑1 activation region that contains Ser167 within a cluster of regulatory serines. The AF‑1 domain harbors Ser104, Ser106, Ser118, and Ser167, and phosphorylation at these residues modulates ERα transcriptional output by altering receptor conformation, chromatin association, and coactivator recruitment, with Ser167 acting as a key node for cross-talk between estrogen and kinase pathways such as mTOR/S6K1, MAPK/p90RSK, Akt, and IKKϵ. Kinases activated downstream of growth factor receptors and oncogenic signaling, including S6K1, RSK, Akt, and IKKϵ, directly phosphorylate Ser167, which enhances ERα-dependent transcriptional activity and supports estrogen-responsive gene expression even under conditions of low ligand, thereby promoting cell-cycle progression and proliferation in ERα-positive tumor cells. Site-specific modulation of Ser167 phosphorylation shapes the temporal pattern of ERα and coactivator complex recruitment to estrogen-responsive promoters and influences the spectrum of target genes that control growth, survival, migration, and invasion, so that Ser167 acts not only as a binary activation mark but also as a determinant of transcriptional programs linked to tumor behavior and therapeutic response. Phosphorylation of Ser167 correlates with activation of upstream MAPK and S6K1 pathways and with increased nuclear accumulation of phospho-ERα, highlighting its position as a downstream readout of mitogenic kinase activity and as a convergence point where growth factor and estrogen signals cooperate to maintain ERα-driven transcription. Clinical analyses of ERα-positive breast cancers show that detection of ERα phosphorylated on Ser167 associates with response to endocrine therapy and with improved post-relapse survival in metastatic settings, indicating that this modification marks tumors that retain functional ER signaling capacity even in the presence of endocrine agents. At the same time, persistent or kinase-driven Ser167 phosphorylation contributes to ligand-independent ERα activation and to resistance mechanisms against tamoxifen and other endocrine treatments, as growth factor–dependent phosphorylation sustains ERα target gene transcription despite receptor antagonism and links phospho-Ser167 status to poor prognosis in subsets of hormone-dependent malignancies, including breast and endometrial cancers.

References
https://pubmed.ncbi.nlm.nih.gov/16168121/ https://pubmed.ncbi.nlm.nih.gov/25597633/

Reference Table for Selecting PVDF Membrane Pore Size Specifications

Protein Size (kDa)	PVDF Transfer Membrane Pore Size (μm)
< 10	0.22
10-20	0.22
20-30	0.45
30-45	0.45
45-70	0.45
80-100	0.45
100-140	0.45
> 140	0.45

Tech Support

Handling Instructions

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

Protein Size (kDa)	Separating Gel Percentage
4-40	20%
12-45	15%
10-70	12.5%
15-100	10%
25-100	8%
60-210	5%