GPR31 Membrane Protein Introduction

Introduction of GPR31

GPR31 is encoded by the GPR31 gene. It belongs to the G-protein-coupled receptor (GPCR) family which is the largest and most diverse group of membrane receptors family in eukaryotes. GPR31 is also known as 112-(S)-hydroxy-5,8,10,14-eicosatetraenoic acid receptor because GPR31 can bind with 12-(S)-HETE with high affinity. GPR31 possess seven transmembrane alpha helices and use 12-(S)-HETE as the preferred endogenous agonist. It is identified using a chemokine receptor-like probe to screen of a human genomic library.

Function of GPR31 Membrane Protein

GPR31 belongs to the oxoeicosanoid G-protein-coupled receptor subfamily. Like other oxoeicosanoid receptors, GPR31 activates the MEK-ERK1/2 and NFκB intercellular signaling pathway, which mediate the responses of PC-3 prostate cancer cells to 12(S)-HETE. GPR31 plays a role in the growth-promoting and metastasis-promoting actions. GPR31 is 12-(S)-HETE receptor with high affinity. 12-(S)-HETE plays an important role in regulating various biological functions. For example, 12-(S)-HETE have been proved to increases the invasiveness and metastatic potential in prostate tumors. Furthermore, 12-(S)-HETE is involved in the carcinogenesis of prostate tumors. Given the various biological function of 12-(S)-HETE, GPR31 is viewed to have many pathophysiological roles along with 12-(S)-HETE by 12-(S)-HETE/GPR31 signaling pathway. However, the biological functions of 12-(S)-HETE/GPR31 signaling pathway are still unclear, further studies of the GPR31 will offer mechanistic insights into 12-(S)-HETE-regulated signaling pathway, suggesting the potential new therapies for a variety of diseases.

Fig.1 Proposed mechanism of 12-lipoxygenase and GPR31. (Ehses, 2015)

Application of GPR31 Membrane Protein in Literature

1. Zhang X-J., et al. An ALOX12-12-HETE-GPR31 signaling axis is a key mediator of hepatic ischemia-reperfusion injury. Nat. Med. 2017, 24:73-88. PubMed ID: 29227475
   
   

   Authors in this group identify 12-HETE and GPR31 signaling pathway plays a key role in the determination of the hepatic ischemia reperfusion process, suggesting that inhibition the production of 12-HETE may be a promising option to prevent and treat hepatic ischemia reperfusion-induced liver damage.

2. Fehrenbacher N., et al. The G protein-coupled receptor GPR31 promotes membrane association of KRAS. The Journal of Cell Biology. 2017, 216(8):2329-2338. PubMed ID: 28619714
   
   

   This article reveals that GPR31 is required for oncogenic KRAS signaling by acting as a secretory pathway chaperone for KRAS4B. The silencing of GPR31 expression using RNAi method results in slowing the growth of KRAS-dependent tumor cells.

3. Fehrenbacher N., et al. Targeting RAS - will GPR31 deliver us a new path forward? Molecular & Cellular Oncology. 2017, 4(6):e1359228. PubMed ID: 29209647
   
   

   The article reports that GPR31 plays an important role in mediation the proliferation and survival of KRAS-dependent cancer cells, suggesting that GPR31 is a potential therapeutic target for anti-RAS therapy.

4. Guo Y., et al. Identification of the Orphan G Protein-coupled Receptor GPR31 as a Receptor for 12-(S)-Hydroxyeicosatetraenoic Acid. The Journal of Biological Chemistry. 2011, 286(39):33832-33840. PubMed ID: 21712392
   
   

   The authors in this article clone and identify GPR31 is a functional receptor of 12-HETE with high affinity and knocking down GPR31 inhibits the 12-HETE induced cell invasion specifically.

5. Honn K.V., et al. 12-HETER1/GPR31, a high-affinity 12(S)-hydroxyeicosatetraenoic acid receptor, is significantly up-regulated in prostate cancer and plays a critical role in prostate cancer progression. The FASEB Journal. 2016, 30(6):2360-2369. PubMed ID: 26965684
   
   

   This article shows GPR31 is upregulated in prostate cancer significantly and reveals the critical new role of GPR31 in prostate cancer progression, offering a novel druggable target for prostate cancer.

GPR31 Preparation Options

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Reference

1. Ehses J.A. and Donath M. Y. (2015). Targeting 12-lipoxygenase as a novel strategy to combat the effects of inflammation on beta cells in diabetes. Diabetologia. 58(3):425-428.

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