Prostacyclin Receptor Regulation--from Transcription to Trafficking

Overview

Journal Curr Mol Med

Publisher Bentham Science Publishers

Specialty Molecular Biology

Date 2011 Jun 29

PMID 21707517

Citations 10

Authors

C Midgett

J Stitham

K A Martin

J Hwa

Affiliations

Soon will be listed here.

Abstract

The prostacyclin receptor (IP--International Union of Pharmacology nomenclature) is a member of the seven transmembrane G-protein coupled receptor (GPCR) superfamily. Recent concerns with selective and non-selective COX-1/COX-2 inhibition have exposed an important cardioprotective role for IP in preventing atherothrombosis. Receptor dysfunction (genetic variants) or reduced signaling (COX-2 inhibition) in high cardiovascular risk patients leads to increased cardiovascular events. These clinical observations have also been confirmed genetically by mouse knockout studies. Thus, receptor regulation is paramount in ensuring correct function in the prevention of atherothrombosis. This review summarizes recent literature on how this important receptor is regulated, from transcription to transport (to and from the membrane surface). These regulatory processes are critical in ensuring that IP receptors are adequately expressed and functional on the cell surface.

Citing Articles

Future Perspectives of Pulmonary Arterial Hypertension: A Review of Novel Pipeline Treatments and Indications.

Novara M, Di Martino E, Stephens B, Nayrouz M, Vitulo P, Carollo A Drugs R D. 2024; 24(1):13-28.

PMID: 38514585 PMC: 11035521. DOI: 10.1007/s40268-024-00453-x.

The oxylipin analog CS585 prevents platelet activation and thrombosis through activation of the prostacyclin receptor.

Stanger L, Yamaguchi A, Yalavarthi P, Lambert S, Gilmore D, Rickenberg A Blood. 2023; 142(18):1556-1569.

PMID: 37624927 PMC: 10656727. DOI: 10.1182/blood.2023020622.

Prostacyclin Released by Cancer-Associated Fibroblasts Promotes Immunosuppressive and Pro-Metastatic Macrophage Polarization in the Ovarian Cancer Microenvironment.

Sommerfeld L, Knuth I, Finkernagel F, Pesek J, Nockher W, Jansen J Cancers (Basel). 2022; 14(24).

PMID: 36551640 PMC: 9776493. DOI: 10.3390/cancers14246154.

Associations of Gut Microbiota and Fatty Metabolism With Immune Thrombocytopenia.

Yu X, Zheng Q, He Y, Yu D, Chang G, Chen C Front Med (Lausanne). 2022; 9:810612.

PMID: 35665326 PMC: 9160917. DOI: 10.3389/fmed.2022.810612.

Glomerular Biomechanical Stress and Lipid Mediators during Cellular Changes Leading to Chronic Kidney Disease.

Sharma M, Singh V, Sharma R, Koul A, McCarthy E, Savin V Biomedicines. 2022; 10(2).

PMID: 35203616 PMC: 8962328. DOI: 10.3390/biomedicines10020407.

References

Grosser T, Bonisch D, Zucker T, Schror K . Iloprost-induced inhibition of proliferation of coronary artery smooth muscle cells is abolished by homologous desensitization. Agents Actions Suppl. 1995; 45:85-91. DOI: 10.1007/978-3-0348-7346-8_13. View

Reid H, Mulvaney E, Turner E, Kinsella B . Interaction of the human prostacyclin receptor with Rab11: characterization of a novel Rab11 binding domain within alpha-helix 8 that is regulated by palmitoylation. J Biol Chem. 2010; 285(24):18709-26. PMC: 2881795. DOI: 10.1074/jbc.M110.106476. View

Marchese A, Raiborg C, Santini F, Keen J, Stenmark H, Benovic J . The E3 ubiquitin ligase AIP4 mediates ubiquitination and sorting of the G protein-coupled receptor CXCR4. Dev Cell. 2003; 5(5):709-22. DOI: 10.1016/s1534-5807(03)00321-6. View

Hayes J, Lawler O, Walsh M, Kinsella B . The prostacyclin receptor is isoprenylated. Isoprenylation is required for efficient receptor-effector coupling. J Biol Chem. 1999; 274(34):23707-18. DOI: 10.1074/jbc.274.34.23707. View

Kobayashi T, Ushikubi F, Narumiya S . Amino acid residues conferring ligand binding properties of prostaglandin I and prostaglandin D receptors. Identification by site-directed mutagenesis. J Biol Chem. 2000; 275(32):24294-303. DOI: 10.1074/jbc.M002437200. View

Massberg S, Brand K, Gruner S, Page S, Muller E, Muller I . A critical role of platelet adhesion in the initiation of atherosclerotic lesion formation. J Exp Med. 2002; 196(7):887-96. PMC: 2194025. DOI: 10.1084/jem.20012044. View

Jaschonek K, Faul C, Schmidt H, Renn W . Desensitization of platelets to iloprost. Loss of specific binding sites and heterologous desensitization of adenylate cyclase. Eur J Pharmacol. 1988; 147(2):187-96. DOI: 10.1016/0014-2999(88)90777-7. View

Lohse M . Dimerization in GPCR mobility and signaling. Curr Opin Pharmacol. 2009; 10(1):53-8. DOI: 10.1016/j.coph.2009.10.007. View

Wilson S, Smyth E . Internalization and recycling of the human prostacyclin receptor is modulated through its isoprenylation-dependent interaction with the delta subunit of cGMP phosphodiesterase 6. J Biol Chem. 2006; 281(17):11780-6. DOI: 10.1074/jbc.M513110200. View

10.

Cottrell G, Padilla B, Pikios S, Roosterman D, Steinhoff M, Gehringer D . Ubiquitin-dependent down-regulation of the neurokinin-1 receptor. J Biol Chem. 2006; 281(38):27773-83. DOI: 10.1074/jbc.M603369200. View

11.

Fisch A, Tobusch K, Veit K, Meyer J, Darius H . Prostacyclin receptor desensitization is a reversible phenomenon in human platelets. Circulation. 1997; 96(3):756-60. DOI: 10.1161/01.cir.96.3.756. View

12.

Smyth E, Li W, FitzGerald G . Phosphorylation of the prostacyclin receptor during homologous desensitization. A critical role for protein kinase c. J Biol Chem. 1998; 273(36):23258-66. DOI: 10.1074/jbc.273.36.23258. View

13.

Ferguson S . Phosphorylation-independent attenuation of GPCR signalling. Trends Pharmacol Sci. 2007; 28(4):173-9. DOI: 10.1016/j.tips.2007.02.008. View

14.

Kinsella B, OMahony D, FitzGerald G . The human thromboxane A2 receptor alpha isoform (TP alpha) functionally couples to the G proteins Gq and G11 in vivo and is activated by the isoprostane 8-epi prostaglandin F2 alpha. J Pharmacol Exp Ther. 1997; 281(2):957-64. View

15.

Kam Y, Chow K, Wise H . Factors affecting prostacyclin receptor agonist efficacy in different cell types. Cell Signal. 2001; 13(11):841-7. DOI: 10.1016/s0898-6568(01)00210-8. View

16.

Smyth E, Austin S, Reilly M, FitzGerald G . Internalization and sequestration of the human prostacyclin receptor. J Biol Chem. 2000; 275(41):32037-45. DOI: 10.1074/jbc.M003873200. View

17.

Wilson S, Dowling J, Zhao L, Carnish E, Smyth E . Regulation of thromboxane receptor trafficking through the prostacyclin receptor in vascular smooth muscle cells: role of receptor heterodimerization. Arterioscler Thromb Vasc Biol. 2006; 27(2):290-6. DOI: 10.1161/01.ATV.0000252667.53790.4e. View

18.

OBrien E, Alpers C, STEWART D, Ferguson M, Tran N, Gordon D . Proliferation in primary and restenotic coronary atherectomy tissue. Implications for antiproliferative therapy. Circ Res. 1993; 73(2):223-31. DOI: 10.1161/01.res.73.2.223. View

19.

Kelly E, Bailey C, Henderson G . Agonist-selective mechanisms of GPCR desensitization. Br J Pharmacol. 2007; 153 Suppl 1:S379-88. PMC: 2268061. DOI: 10.1038/sj.bjp.0707604. View

20.

Milligan G . G protein-coupled receptor dimerization: function and ligand pharmacology. Mol Pharmacol. 2004; 66(1):1-7. DOI: 10.1124/mol.104.000497.. View