antibody

Anti-Phospho-Ser294 Progesterone Receptor

MBS500012

0.1 mL

345 USD

monoclonal

mouse

nonconjugated

phosphorylated

608

western blot, immunohistochemistry

Antibody

Anti-Phospho-Ser294 Progesterone Receptor

Progesterone Receptor (Ser294)

progesterone receptor isoform B; Progesterone receptor; progesterone receptor; nuclear receptor subfamily 3 group C member 3; progesterone receptor; Nuclear receptor subfamily 3 group C member 3

PGR

PGR; PGR; PR; NR3C3; NR3C3; PR

PRGR_HUMAN

Monoclonal

IgG1

608

Mouse

Human

933

Specific for the ~90k PR-A isoform and the ~120k PR-B isoform phosphorylated at Ser294. Immunolabeling is blocked by the phosphopeptide used as the antigen but not by the corresponding dephosphopeptide.

Protein G purified (Prepared by affinity purification using a protein G column.)

100 ul in 10 mM HEPES (pH 7.5), 150 mM NaCl, 100 ug per ml BSA and 50% glycerol. Adequate amount of material to conduct 10-mini Western Blots.

For long term storage -20 degree C is recommended. Stable at -20 degree C for at least 1 year.

Western Blot (WB), Immunohistochemistry (IHC)

Quality Control: Western blots performed on each lot. WB: 1:1000. IHC (frozen sections; unpublished observations): 1:1000

Antigen: Phosphopeptide corresponding to amino acid residues surrounding the phospho-Ser294 of human progesterone receptor. Immunogen Information: Synthetic phospho-peptide corresponding to amino acid residues surrounding Ser294 conjugated to KLH. Immunogen Species: Human

Reactivity Assumed Based on 100% Sequence Homology: Non-human primates. Species Reactivity Note: The antibody has been directly tested for reactivity in Western blots with human tissue. It is anticipated that the antibody will also react with non-human primates based on the fact that these species have 100% homology with the amino acid sequence used as antigen. Biological Significance: There is accumulating evidence to suggest that progesterone plays an essential role in the regulation of growth and differentiation of mammary glands and thus may play a key role in breast cancer (Edwards, 2005). The biological response to progesterone is mediated by two distinct forms of the human progesterone receptor (PR-A and PR-B forms). In most cell contexts, the B form functions as a transcriptional activator, whereas the A form functions as a transcriptional inhibitor of steroid hormones (Attia et al., 2000; Lin et al., 2003). Recently it has been demonstrated that there is differential hormone dependent regulation of the phosphorylation of the A and B forms of the receptor (Clemm et al., 2000). Treatment of T47D breast cancer cells with progestin agonist increases the phosphorylation of Ser190 and Ser294 with different kinetics. These phosphorylation events may differentially affect the transcriptional activity of the receptor.

Affinity purified mouse monoclonal antibody

Attia GR, Zeitoun K, Edwards D, Johns A, Carr BR, Bulun SE (2000) Progesterone receptor isoform A but not B is expressed in endometriosis. J Clin Endocrinol Metab 85:2897-2902. Clemm DL, Sherman L, Boonyaratanakornkit V, Schrader WT, Weigel NL, Edwards DP (2000) Differential hormone-dependent phosphorylation of progesterone receptor A and B forms revealed by a phosphoserine site-specific monoclonal antibody. Mol Endocrinol 14:52-65. Edwards DP (2005) Regulation of signal transduction pathways by estrogen and progesterone. Annu Rev Physiol 67:335-376. Lin VC, Woon CT, Aw SE, Guo C (2003) Distinct molecular pathways mediate progesterone-induced growth inhibition and focal adhesion. Endocrinology 144:5650-5657.

110611914

NP_000917.3

NM_000926.4

P06401

90/120

Cellular Roles Of Anthrax Toxin Pathway (138076); Gene Expression Pathway (105937); Generic Transcription Pathway (105938); Nuclear Receptor Transcription Pathway (105979); Nuclear Receptors Pathway (198848); Nuclear Signaling By ERBB4 Pathway (530744); Oocyte Meiosis Pathway (126909); Oocyte Meiosis Pathway (126872); Ovarian Infertility Genes Pathway (198801); Progesterone-mediated Oocyte Maturation Pathway (119304)

This gene encodes a member of the steroid receptor superfamily. The encoded protein mediates the physiological effects of progesterone, which plays a central role in reproductive events associated with the establishment and maintenance of pregnancy. This gene uses two distinct promotors and translation start sites in the first exon to produce two isoforms, A and B. The two isoforms are identical except for the additional 165 amino acids found in the N-terminus of isoform B and mediate their own response genes and physiologic effects with little overlap. [provided by RefSeq, Jan 2011]

Function: The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Progesterone receptor isoform B (PRB) is involved activation of c-SRC/MAPK signaling on hormone stimulation. Ref.12 Ref.20 Ref.21 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27Isoform A:inactive in stimulating c-Src/MAPK signaling on hormone stimulation. Ref.12 Ref.20 Ref.21 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27Isoform 4:Increases mitochondrial membrane potential and cellular respiration upon stimulation by progesterone. Ref.12 Ref.20 Ref.21 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27. Subunit structure: Interacts with SMARD1 and UNC45A. Interacts with CUEDC2; the interaction promotes ubiquitination, decreases sumoylation, and repesses transcriptional activity. Interacts with PIAS3; the interaction promotes sumoylation of PR in a hormone-dependent manner, inhibits DNA-binding, and alters nuclear export. Interacts with SP1; the interaction requires ligand-induced phosphorylation on Ser-345 by ERK1/2 MAPK. Interacts with PRMT2. Ref.18 Ref.19 Ref.22 Ref.23 Ref.24 Ref.27. Subcellular location: Nucleus. Cytoplasm. Note: Nucleoplasmic shuttling is both homone- and cell cycle-dependent. On hormone stimulation, retained in the cytoplasm in the G1 and G2/M phases. Ref.12 Ref.20 Ref.21 Ref.26Isoform A: Nucleus. Cytoplasm. Note: Mainly nuclear. Ref.12 Ref.20 Ref.21 Ref.26Isoform 4: Mitochondrion outer membrane Ref.12 Ref.20 Ref.21 Ref.26. Domain: Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain. Post-translational modification: Phosphorylated on multiple serine sites. Several of these sites are hormone-dependent. Phosphorylation on Ser-294 occurs preferentially on isoform B, is highly hormone-dependent and modulates ubiquitination and sumoylation on Lys-388. Phosphorylation on Ser-102 and Ser-345 also requires induction by hormone. Basal phosphorylation on Ser-81, Ser-162, Ser-190 and Ser-400 is increased in response to progesterone and can be phosphorylated in vitro by the CDK2-A1 complex. Increased levels of phosphorylation on Ser-400 also in the presence of EGF, heregulin, IGF, PMA and FBS. Phosphorylation at this site by CDK2 is ligand-independent, and increases nuclear translocation and transcriptional activity. Phosphorylation at Ser-162 and Ser-294, but not at Ser-190, is impaired during the G2/M phase of the cell cycle. Phosphorylation on Ser-345 by ERK1/2 MAPK is required for interaction with SP1. Ref.11 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.20 Ref.21 Ref.25 Ref.26 Ref.27Sumoylation is hormone-dependent and represses transcriptional activity. Sumoylation on all three sites is enhanced by PIAS3. Desumoylated by SENP1. Sumoylation on Lys-388, the main site of sumoylation, is repressed by ubiquitination on the same site, and modulated by phosphorylation at Ser-294. Ref.23 Ref.24 Ref.25Ubiquitination is hormone-dependent and represses sumoylation on the same site. Promoted by MAPK-mediated phosphorylation on Ser-294. Ref.23 Ref.24 Ref.25Palmitoylated by ZDHHC7 and ZDHHC21. Palmitoylation is required for plasma membrane targeting and for rapid intracellular signaling via ERK and AKT kinases and cAMP generation. Ref.28. Sequence similarities: Belongs to the nuclear hormone receptor family. NR3 subfamily.Contains 1 nuclear receptor DNA-binding domain.

0.1 mL

345 USD