P2RY8 Membrane Protein Introduction

Introduction of P2RY8

P2RY8 is encoded by the P2RY8 gene. It belongs to the G-protein-coupled receptor (GPCR) family which is the largest family of membrane-bound receptors and also the targets of many drugs. It is one of the nigh subtypes of purinergic receptors (P2RY1, P2RY2, P2RY4, P2RY6, P2RY8, P2RY11, P2RY12, P2RY13, and P2RY14). P2RY8 possesses seven transmembrane alpha helices as other GPCRs and is activated by adenosine and uridine nucleotides. However, the expression profile of P2RY8 has been rarely documented in humans.

Function of P2RY8 Membrane Protein

P2RY8 functions as a transmembrane receptor, which preferentially binds to, and is activated by, adenosine and uridine nucleotides. The activity of P2RY8 is activated by adenosine and uridine nucleotides resulting in evoking the activation of adenylyl cyclase intracellular signaling pathway. Upon binding to nucleotides, P2RY8 can activate the extracellular signal-regulated kinases signaling pathway and the activation of phospholipase C. There are also some research papers show that the purinergic receptor signaling is involved in a variety of cellular responses, such as cell differentiation, cell migration, cell growth, and cell apoptosis. When it comes to screen the downstream components of P2RY8 signaling pathway in cells, the CREB and Elk-1 are activated by P2RY8, and the expression level of P2RY8 is upregulated after activation. Meanwhile, the transcriptional activities of the SRE, the c-Fos and c-Myc are regulated by P2RY8. The patients with a high expression level of P2RY8 have a higher risk of leukemogenesis than those with a lower expression level of P2RY8, so P2RY8 may have a contribution to leukemogenesis.

Fig.1 Schematic overview of the various mechanisms of P2RY membrane proteins. (Hechler, 2015).

Application of P2RY8 Membrane Protein in Literature

1. Fujiwara S-I., et al. Transforming activity of purinergic receptor P2Y, G protein coupled, 8 revealed by retroviral expression screening. Leuk Lymphoma. 2007, 48(5):978-986. PubMed ID: 17487742
   
   

   This article reports that P2RY8 has a possible contribution to the formation of leukemogenesis because of the higher expression level of P2RY8 in leukemia patients. P2RY8 may be a potential drug target for the treatment of leukemia.

2. Dou H., et al. Prognostic significance of P2RY8-CRLF2 and CRLF2 overexpression may vary across risk subgroups of childhood B-cell acute lymphoblastic leukemia. Genes Chromosomes Cancer. 2016, 56(2):135-146. PubMed ID: 27637012
   
   

   This article reveals that P2RY8-CRLF2 fusion protein is an important indicator to the B-cell acute lymphoblastic leukemia because the expression pattern of P2RY8-CRLF2 fusion protein is correlated with the occurrence rate of B-cell acute lymphoblastic leukemia.

3. Morak M., et al. Small sizes and indolent evolutionary dynamics challenge the potential role of P2RY8-CRLF2–harboring clones as main relapse-driving force in childhood ALL. Blood. 2012, 120(26):5134-5142. PubMed ID: 23091296
   
   

   Authors in this group apply the genomic quantification method to analyze the P2RY8-CRLF2 positive leukemias, and the expression of P2RY8-CRLF2 fusion protein increases in B-cell precursor acute lymphoblastic leukemia patients.

4. Palmi C., et al. Poor prognosis for P2RY8-CRLF2 fusion but not for CRLF2 over-expression in children with intermediate risk B-cell precursor acute lymphoblastic leukemia. Leukemia. 2012, 26:2245. PubMed ID: 22484421
   
   

   This article focuses on the pharmacological role of P2RY8-CRLF2 fusion protein in pediatric B-cell precursor acute lymphoblastic leukemia and suggests that P2RY8-CRLF2 fusion protein is the most relevant prognostic factor in CRLF2 overexpression pediatric B-cell precursor acute lymphoblastic leukemia patients.

5. Storlazzi C.T., et al. Upregulation of the SOX5 by promoter swapping with the P2RY8 gene in primary splenic follicular lymphoma. Leukemia. 2007, 21:2221. PubMed ID: 17554380
   
   

   This article evaluates the overexpression of SOX5 is regulated by the P2RY8 promoter and the further studies indicate that SOX5 gene expression may be involved in the pathogenesis of primary splenic follicular lymphoma.

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Reference

1. Hechler B & Gachet C. (2015). Purinergic Receptors in Thrombosis and Inflammation. Atertio. Thromb. Vasc. Biol. 35(11):2307-2317.

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