Disease relevance of EPR1

• Downregulation of survivin expression by induction of the effector cell protease receptor-1 reduces tumor growth potential and results in an increased sensitivity to anticancer agents in human colon cancer [1].
• The positive rate of EPR-1 expression in the primary gastric adenocarcinomas, invasion tumor node and lymph node metastasis was 65.83%, 55.29% and 68%, respectively [2].
• However, the average AI in EPR-1-positive lymph node metastasis tumors was 0.99%, which was significantly higher than that of 0.67% observed in EPR-1-negative lymph node metastasis [2].
• In contrast, several non-Hodgkin's lymphomas, or the nonneoplastic cellular components of HD, did not react with anti-EPR-1 monoclonal antibodies [3].
• Protease receptors in Hodgkin's disease: expression of the factor Xa receptor, effector cell protease receptor-1, in Reed-Sternberg cells [3].

High impact information on EPR1

• Here we report that targeting a factor Xa receptor, designated effector cell protease receptor-1 (EPR-1), with antisense oligonucleotide or with a monoclonal antibody (mAB 2E1) inhibited CD3/T-cell receptor-dependent lymphocyte proliferation [4].
• 125I-factor Xa binding was not affected by factor X, thrombin, or by DX9065, a direct inhibitor of factor Xa, but was inhibited by factor Xa (IC50 = 5.4+/-0.2 nM; n = 9) and by antibodies specific for the effector cell protease receptor 1 (EPR-1), a well-known receptor of factor Xa on various cell types [5].
• When applied locally to air-injured rabbit carotid arteries, antibodies directed against EPR-1 (100 mug/ artery) strongly reduced myointimal proliferation 14 d after vascular injury (65-71% inhibition, P < 0.01) [5].
• These findings indicate that SMCs express functional high affinity receptors for factor Xa related to EPR-1, which may be of importance in the regulation of homeostasis of the vascular wall and after vascular injury [5].
• ECFC from patients with secondary (EP driven) polycythemia or anemia show two classes of EP-R (Kd = 0.18 and 1.10 nM, respectively) [6].

Biological context of EPR1

• Splicing of the intervening sequence occurs in a cell type-specific fashion, as judged by the constitutive membrane overexpression of EPR-1 in certain leukemic B lymphocytes and monocytic cells [7].
• One of the cellular binding sites for factor Xa, designated effector cell protease receptor-1 (EPR-1), has recently emerged as a novel potential regulator of factor Xa-mediated mitogenic signaling [8].
• These findings suggest the existence of a potential EPR-1/survivin gene cluster and identify survivin as a new target for disrupting cell viability pathways in cancer [9].
• Transient co-transfection of an EPR-1 cDNA potentially acting as a Survivin antisense with a lacZ reporter plasmid resulted in loss of viability of HeLa cells [9].
• Weighted EPR-1 Score is positively correlated with apoptosis index, but is negatively related with proliferative index [2].

Anatomical context of EPR1

• Monoclonal antibodies were generated against EPR-1+ MOLT13 lymphocytes and selected for reactivity with lymphocyte surface proteins by flow cytometry and with affinity-purified EPR-1 in Western blots [10].
• Binding of the coagulation protease factor Xa to leukocytes is contributed by a recently identified molecule, denominated Effector cell Protease Receptor-1 (EPR-1) [10].
• Furthermore, phenotypic analysis of cell lines stably transfected with functionally spliced or unspliced EPR-1 constructs suggests a potential role of intron cis-acting sequence(s) in splicing regulation [7].
• In stably transfected HeLa cells, ZnSO4 induction of an EPR-1 mRNA under the control of a metallothionein promoter suppressed the expression of endogenous survivin [9].
• In Northern blots, a single strand-specific probe identified a 1.3-kb EPR-1 mRNA broadly distributed in normal adult and fetal tissues, structurally distinct from the 1.9-kb Survivin transcript expressed in transformed cell lines [9].

Associations of EPR1 with chemical compounds

• Effector cell protease receptor-1 (EPR-1) is a transmembrane glycoprotein receptor for factor Xa that contributes to cell surface assembly of proteolytic activities and leukocyte mitogenesis [7].
• This strategy identified a monoclonal antibody (MAb) (EPR1) that blocks binding of titanium dioxide (TiO(2)) particles to the EC line which served as the immunogen (A549), as well as to other EC lines (Beas 2-B, HTB54, HeLa, and MDA-MB-435S) [11].
• 125I-Labeled Factor Xa bound to endothelial cells in a dose-dependent saturable manner, and the binding was inhibited by antibody to EPR-1 [12].
• Effector cell protease receptor (EPR-1) was identified as a novel leukocyte cell surface receptor recognizing the coagulation serine protease Factor Xa but not the precursor Factor X [12].
• Factor Xa or catalytically inactive 5-dimethylaminonaphthalene-1sulfonyl (dansyl) Glu-Gly-Arg-(DEGR)-chloromethylketone-factor Xa bound indistinguishably to HUVEC and EPR-1 transfectants, and inhibited equally well the binding of 125I-factor Xa to these cells [13].

Regulatory relationships of EPR1

• [125I]-factor Xa binding was inhibited by factor Xa but was not affected by factor X, thrombin or monoclonal antibodies against factor V, antithrombin-III or tissue factor pathway inhibitor (TFPI) but was inhibited by an antibody specific for the effector cell protease receptor-1 (EPR-1), a well-known receptor of factor Xa on various cell types [14].
• These results suggest that EP receptor subtypes regulate acid extrusion mainly via NHE-1 through distinct signal transduction pathways in CHO cells [15].

Other interactions of EPR1

• On the other hand, the average positive labeling index for Ki-67 (ki-67) in EPR-1-positive lymph node metastasis was 7.65%, which was significantly lower than that of 9.44% observed in EPR-1-negative lymph node metastasis [2].
• To clarify the involvement of E-prostanoid (EP) receptors in the effect of prostaglandin E(2) on human monocyte-derived dendritic cell (MoDC) maturation, we examined the effect of four types of EP receptor-selective agonists on MoDC maturation [16].
• These results may suggest that EP4 receptor plays an important role among four EP receptor subtypes for relaxation of smooth muscle in the human corpus cavernosum.International Journal of Impotence Research (2006) 18, 275-281. doi:10.1038/sj.ijir.3901408; published online 20 October 2005 [17].
• Cyclooxygenase-2 (COX-2)-generated Prostaglandin-E(2) (PGE(2)), which signals through the PGE(2) receptor (EP receptor), as well as nitric oxide metabolites (NOx), appear to be important in postoperative immune dysfunction [18].
• In addition to the 62-kDa effector cell protease receptor 1, mAb 2E1 bound the 32-kDa T cell adhesion receptor E2 (CD99) and the 86-kDa p80 subunit of the nuclear antigen complex Ku [19].

Analytical, diagnostic and therapeutic context of EPR1

• Molecular cloning of effector cell protease receptor-1, a novel cell surface receptor for the protease factor Xa [10].
• EPR1 demonstrated specific labeling of ECs using immunohistology techniques and its expression could be quantitated by flow cytometry of permeabilized ECs in suspension [11].
• Expression of EPR-1 transcripts in Reed-Sternberg cells was demonstrated by in situ hybridization with an antisense EPR-1 riboprobe, and by amplification of reverse-transcribed HD RNA with EPR-1-specific primers [3].
• Immunohistochemical analysis demonstrated prominent reactivity of monoclonal antibodies to EPR-1 with Reed-Sternberg cells in 30 of 35 cases of nodular-sclerosis, lymphocyte-depletion, and mixed-cellularity Hodgkin's disease (HD) [3].
• Molecular dissection of effector cell protease receptor-1 recognition of factor Xa. Assignment of critical residues involved in antibody reactivity and ligand binding [20].

References