Recombinant Human Prostaglandin F2-alpha receptor (PTGFR)
Description
Functional Mechanisms
PTGFR couples primarily with Gq proteins, initiating downstream signaling:
Receptor activation increases output of pro-inflammatory cytokines (IL-6, CXCL8, CCL2) in uterine smooth muscle cells while suppressing TNFα . Structural studies reveal PGF2α induces a 6.7 Å outward displacement of TM6 for G protein engagement .
Research Applications
Recombinant PTGFR enables:
-
Drug discovery: Used to develop glaucoma therapeutics like bimatoprost through prostamide receptor complex studies
-
Diagnostic development: Basis for ELISA kits detecting PTGFR in serum/plasma (Detection range: 0.312-20 ng/mL)
-
Mechanistic studies: Cryo-EM structures (2.67-3.14 Å resolution) reveal ligand-binding conformations and Gq coupling interfaces
Available Recombinant Proteins
Commercial sources provide multiple formats:
Key Research Findings
Recent structural and functional insights:
-
Activation mechanism: Q250⁶·³⁶/R308⁸·⁴⁷ hydrogen bond stabilizes active conformation, enabling Gq coupling without traditional ERY motif
-
Pathological roles:
-
Therapeutic targeting: TFPA analog shows 89% receptor occupancy at 10 μM with reduced side effects vs endogenous PGF2α
Technical Considerations
Critical parameters for experimental use:
Product Specs
Note: We prioritize shipping the format currently in stock. However, if you have specific format requirements, please indicate them when placing your order. We will fulfill your request if possible.
Note: Our proteins are typically shipped with standard blue ice packs. If dry ice shipment is required, please communicate your request in advance as additional charges may apply.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.
Target Background
- Data, including data from studies using transgenic mice, suggest that signaling via prostaglandin-F2alpha/PTGFR and Camk2g/p38/Foxo1 MAP kinase/calcium pathways are involved in regulation of hepatic gluconeogenesis in both obesity and fasting. (PTGFR = prostaglandin F2alpha receptor; Camk2g = calcium-calmodulin-dependent protein kinase type 2 gamma; p38 = p38 MAP kinase; Foxo1 = forkhead box transcription factor O1) PMID: 29773555
- Data suggest that allosteric communication between heterodimeric AT1R and PTGFR is mediated through GNAQ and may also involve proximal phospholipase C but not distal protein kinase C signaling partners; PTGFR activation has negligible effects on AT1R-based conformational biosensors. (AT1R = angiotensin II receptor, type 1; PTGFR = prostaglandin F2alpha receptor; GNAQ = GTP-binding protein G[q] subunit alpha) PMID: 28584054
- The genotype frequencies of six SNPs in AFAP1, GMDS and PTGFR genes were conformed to Hardy-Weinberg equilibrium (HWE). PMID: 27862086
- These results indicated that the actions of AKR1C3 can produce FP receptor ligands whose activation results in carcinoma cell survival in breast cancer. PMID: 26170067
- The results indicated that the rs12731181 G allele of the Prostaglandin F2alpha Receptor Gene was associated with susceptibility to essential hypertension. PMID: 25977569
- Influence of PTGS1, PTGFR, and MRP4 genetic variants on intraocular pressure response to latanoprost in Chinese primary open-angle glaucoma patients PMID: 25339146
- The SNPs of the PTGFR and MMP-1 genes may determine the latanoprost response in a white European Spanish population. PMID: 25704319
- Angiotensin II type I and prostaglandin F2alpha receptors cooperatively modulate signaling in vascular smooth muscle cells PMID: 25512374
- An association was found between SNPs of the FP receptor gene and the response to latanoprost in patients with glaucoma or OH. PMID: 24457363
- The results of this study suggested that significant novel association signals near the genes PTGFR, and provide supportive evidence for the previously reported association signals near ANK3 and within the 3p21.1 locus. PMID: 22182935
- The F-prostaglandin receptor is a novel marker for tumor endothelial cells in renal cell carcinoma. PMID: 23356224
- We found no indication for an association between SNPs in the prostaglandin F(2alpha) receptor gene or SLCO2A1 and IOP response to prostaglandin analogs in a population of European descent. PMID: 22060278
- These data demonstrate a role for the FP receptor in regulation of the chemokine CCL20, which can mediate proliferation of endometrial adenocarcinoma epithelial cells. PMID: 20816914
- Data show a labour-associated decrease in PTGFR-v1 and PTGFR transcript variant 2 mRNA expression in lower segment myometrial samples. PMID: 20519365
- Dental pulp cells expressed prostaglandin FP receptors as analyzed by RT-PCR, which showed the presence of 396-bp PCR product. Pulp cells also expressed FP receptor protein (64 kD) as analyzed by Western blotting. PMID: 20536573
- The prostaglandin F(2alpha) can directly regulate endothelial cell network formation but not endothelial cell proliferation. PMID: 20092633
- This study investigated the expression of IL-11 and role of prostaglandin F(2alpha)-F-prostanoid receptor (FP receptor) signaling in the modulation of IL-11 expression in endometrial adenocarcinoma cells. PMID: 20008143
- Our data have elucidated the molecular and cellular mechanism whereby PGF(2alpha) regulates CXCL8 expression via the FP receptor in endometrial adenocarcinomas and have highlighted RCAN1-4 as a negative regulator of CXCL8 expression PMID: 19819266
- Identification of amino acids contributing to ligand specificity or signal transduction properties of this protein PMID: 12519077
- Isolation and sequencing of 4106-bp promoter DNA fragment that contains -2436-bp of 5'-flanking sequence; identification of transcription initiation start site PMID: 14746914
- PGF(2 alpha)-FP receptor may promote endometrial tumorigenesis via phospholipase C-mediated phosphorylation of EGF receptor and MAPK signaling pathways. PMID: 14764825
- Prostaglandin F2alpha production is stimulated by withdrawal of ovarian steroids through nuclear factor-kappaB activation via oxygen radicals PMID: 15118249
- Alterations in the amino acid sequence of the C-terminal domain of PTGFR and their effects on GTP-binding protein signaling are reported. PMID: 15651980
- The regulation of the FP receptor and the stimulation of production of PGF2alpha in melanocytes in response to ultraviolet radiation suggest that PGF2alpha could act as an autocrine factor for melanocyte differentiation. PMID: 15748887
- Uteroglobin plays important roles in maintaining homeostasis in organs that are vulnerable to inadvertent stimulation of FP-mediated inflammatory response by inhibiting the prostaglandin F2alpha receptor PMID: 16061484
- FP receptor activation of Rho signaling by PGF(2alpha) can interfere with nuclear division PMID: 16378246
- NFkappaB is involved in both basal and interleukin 1beta-stimulated transcription of the PTGFR gene. PMID: 16855208
- Level at term may facilitate the decidua contribution to parturition, and its regulation and role should be examined further. PMID: 16911823
- rs3753380 and rs3766355, SNPs in the promoter and intron 1 regions of the FP receptor gene, correlate with a response to short-term latanoprost treatment in normal volunteers. PMID: 17467803
- Role for PGF(2alpha)-FP receptor interaction in modulating FGF2 expression and signaling using an endometrial adenocarcinoma cell line PMID: 17478553
- A novel PGF2alpha receptor single nucleotide polymorphism (SNP), IVS -97A>T, is common in the Malaysian patients with glaucoma. PMID: 17582204
- Data show that prostaglandins E2 and F2alpha can mobilize inositol 1,4,5-trisphosphate, induce ERK1/2 phosphorylation and induce cyclooxygenase-2 expression via the FP receptor. PMID: 18316157
- Bimatoprost lacks effects on the FP receptor but may interact with the FP-altFP receptor heterodimer to induce alterations in second messenger signaling. PMID: 18587449
- FPR signaling mechanism(s) regulating MLC-2 phosphorylation likely extend beyond those classically established for G(q/11)-coupled receptors PMID: 18703533
- Urinary 8-iso-prostaglandin excretion is enhanced in microalbuminuric compared to nonmicroalbuminuric hypertensive patients or controls PMID: 19280705
- Expression and functional evidence of the PTGFR mediating contraction in human umbilical vein are reported. PMID: 19289115
- Oxytocin, its receptor and the PGF(2alpha) receptor are involved in the regulation of labour through a paracrine mechanism. PMID: 19347709
- The rabbit prostaglandin F receptor (FP) couples to the inhibitory G protein, Gi, to inhibit vasopressin action in the cortical collecting duct. PMID: 16096282
Q&A
Basic Research Questions
-
What is the structure and function of human PTGFR?
PTGFR is a seven-transmembrane G protein-coupled receptor encoded by the PTGFR gene in humans. The full-length receptor consists of 359 amino acids . PTGFR functions as the receptor for prostaglandin F2α (PGF2α), playing pivotal roles in regulating inflammation, allergic responses , and reproductive processes such as luteolysis . Structural analysis via cryo-EM has revealed high-quality density maps for the receptor at resolutions of 2.67-3.14 Å, allowing unambiguous model building for receptor structure containing residues 29-323 . The receptor has distinct binding domains, with the carboxylate-containing α-chain binding to subpockets with highly conserved residues, while the F ring provides receptor selectivity .
-
What signaling pathways are activated by PTGFR?
PTGFR primarily couples to Gq/G11 family proteins, leading to phospholipase C stimulation . Upon activation, this triggers the phosphatidylinositol-calcium second messenger system . The signaling cascade includes:
-
Elevation of intracellular Ca²⁺ concentration mediated by PKC phosphorylation
-
Activation of the MAPK1/3 pathway, potentially elevating expression of angiogenic factors
Functional assays have demonstrated dose-dependent increases in total inositol phosphate accumulation and intracellular calcium release in human trabecular meshwork cells consistent with PTGFR activation . These signaling events ultimately lead to physiological responses such as smooth muscle contraction .
-
-
How can PTGFR expression be detected in experimental settings?
Multiple complementary approaches have been validated for detecting PTGFR:
-
Immunofluorescence microscopy: Utilizing affinity-purified antibodies raised against GST-FPA receptor fusion proteins to visualize receptor localization in tissue sections and cultured cells .
-
RT-PCR: Using primers specific for PTGFR mRNA (e.g., forward: GAGGTTGATGTCGAGCA; reverse: TTGTTCATACGTGTAGC for human PTGFR) to detect receptor expression, with normalization to housekeeping genes like ACTB.
-
Functional assays: Measuring PGF2α-stimulated inositol phosphate hydrolysis and intracellular calcium measurements to confirm functional receptor presence .
-
Western blotting: Using validated antibodies to detect PTGFR protein in cell and tissue lysates .
Cross-validation with multiple techniques is recommended, as demonstrated in studies where receptor presence was confirmed by mRNA, protein, and functional response to PGF2α .
-
-
What are the binding affinities of various ligands for PTGFR?
PTGFR demonstrates selective binding affinities for various prostanoids, with PGF2α being the principal endogenous agonist. The relative binding affinities are expressed as Ki values (nM):
Receptor/cell line PGF2α PGE2 PGD2 Reference hDP1/HEK293 861±139 307±106 1.7±0.3 Sawyer et al. 2002 DP/human platelets 18,000±6,400 11,000±2,100 80±5 Sharif et al. 2000b The potency order of endogenous ligands is: PGF2α > PGD2 > PGE2 > PGI2, thromboxane A2 . PGF2α has approximately 12-fold higher affinity for the FP receptor compared to the EP3 receptor, while PGE2 has around 360-fold higher affinity for EP3 compared to FP .
-
What experimental models are suitable for studying PTGFR function?
Several validated experimental models have been used to study PTGFR:
-
Recombinant expression systems: Heterologous expression in HEK-293 cells , wheat germ cell-free protein synthesis systems , and other mammalian cell lines provides controlled environments for studying receptor properties.
-
Primary cell cultures: Human trabecular meshwork cells , luteinizing granulosa cells , and preadipocytes have been used to study endogenous PTGFR function in relevant physiological contexts.
-
Tissue explants: Ovarian tissues from female cynomolgus monkeys and human endometrial explants have been employed to study PTGFR in intact tissue environments.
-
Purified receptor systems: Recombinant PTGFR proteins with various tags (His, GST, Strep) are available for in vitro binding and structural studies .
Each model has specific advantages depending on the research question, with cell-based systems offering reproducibility and primary tissues providing physiological relevance.
-
