PROKR2 Membrane Protein Introduction

Introduction of PROKR2

PROKR2 is encoded by the PROKR2 gene. It belongs to the G-protein-coupled receptor (GPCR) family which is the largest single class trans-membrane proteins and is important regulator therapeutic drug targets of human physiology. It is one of the two subtypes of family A GPCRs (PROK1 and PROKR2). Amino acids sequence indicates that PROKR1 and PROKR2 share 85% sequence identity. PROKR2 is composed of 81 amino acids contains 10 cysteines forming five disulfide bridges. No structure of the PROKR1 or PROKR2 has been reported so far.

Function of PROKR2 Membrane Protein

PROKR2 is a G protein-coupled receptor and the activity of PROKR2 is activated by its ligands, prokineticins 2 (PROK2), which belong to the AVIT protein family. The most important function of PROKR2 and its ligand PROK2 signalling pathway is the regulation of the secretion of neurohormone in the mammalian reproductive system. The PROKR2 knockout mice have a failure in GnRH secretion resulting in an impairment of sexual development and fertility in both male and female mice. Kallmann syndrome associated PKR2 mutations fail to bind with its ligand and couple with G protein, resulting in the deficiency in the trafficking onto the cell membrane. The patients caring mutations in PROK2 or PROKR2 genes have both neural and neuroendocrine developmental abnormalities, suggesting that the PROK2/PROKR2 signaling pathway plays an essential role in the embryonic development of the olfactory system. Both PROKR1 and PROKR2 are involved in mediating the releasing of prokineticins in the central and peripheral systems.

Fig.1 PROKR2 intracellular signaling pathways (Traboulsi, 2015)

Application of PROKR2 Membrane Protein in Literature

1. Nebigil C.G. Updates on Endothelial Functions of Proangiogenic Prokineticin. Hypertension. 2016, 68(5):1091. PubMed ID: 27672031
   
   

   This article summarizes the biological functions of prokineticins (PROK) and their receptors (PROKR1 and PROKR1) in endothelial function/dysfunction and discusses the possible therapeutic potential of PROKR1 or PROKR1 in treating the cardiovascular and renal diseases.

2. Traboulsi, W., et al. Prokineticins in central and peripheral control of human reproduction. Hormone Molecular Biology and Clinical Investigation. 2015, 24(2): 73-81. PubMed ID: 26574895
   
   

   This article reviews the function of PROKR1 and PROKR1 in controlling the reproduction of prokineticins. The mutations of PROK2 and PROKR2 are involved in the development of Kallmann syndrome, which is the direct consequence of the abnormality of the reproductive system.

3. Chen D-N., et al. Functional Rescue of Kallmann Syndrome-associated Prokineticin Receptor 2 (PKR2) Mutants Deficient in Trafficking. The Journal of Biological Chemistry. 2014, 289(22):15518-15526. PubMed ID: 24753254
   
   

   Authors in this group demonstrate that the combined treatment of the PROKR2 antagonist and glycerol can rescue the trafficking deficiency associated PROKR2 mutants, suggesting a potential treatment strategy to patients harboring trafficking-defective PROKR2 mutations.

4. Zhou C., et al. (2014) Mild Moxibustion Decreases the Expression of Prokineticin 2 and Prokineticin Receptor 2 in the Colon and Spinal Cord of Rats with Irritable Bowel Syndrome. Evidence-based Complementary and Alternative Medicine: eCAM. 2014, 807308. PubMed ID: 25024732
   
   

   This article reports the important role of prokineticin 2 (PK2) and its receptor PROKR2 in mild moxibustion analgesia in rats with chronic visceral hyperalgesia. The results of this article prove the mild moxibustion can suppress the abnormally increased expression of PK2/PROKR2 in the colon and spinal cord of IBS model rats.

5. Martin C., et al. The Role of the Prokineticin 2 Pathway in Human Reproduction: Evidence from the Study of Human and Murine Gene Mutations. Endocr. Rev. 2011, 32(2):225-246. PubMed ID: 21037178
   
   

   This article shows the detailed clinical studies of patients with PROK2/PROKR2 mutations, suggesting the broader biological role of the PROK2/PROKR2 pathway in humans.

PROKR2 Preparation Options

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Reference

1. Traboulsi, W., et al. (2015) Prokineticins in central and peripheral control of human reproduction. Hormone Molecular Biology and Clinical Investigation, 24(2): 73-81.

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