GPR78 Membrane Protein Introduction

Introduction of GPR78

G-protein coupled receptor 78 (GPR78) is a protein that in humans is encoded by the GPR78 gene. Gene Ontology (GO) annotations associated with this gene include G-protein coupled receptor activity. An important paralog of this gene is GPR26. GPR78 is a member of the G protein-coupled receptor family. G protein-coupled receptors contain 7 transmembrane domains and transduce extracellular signals through heterotrimeric G proteins. GPR78 is currently considered to be an orphan receptor that displays a significant level of constitutive activity. The effects of GPR78 are mediated by G(s)-alpha protein that stimulates adenylate cyclase, leading to an elevation of intracellular cAMP.

Function of GPR78 Membrane Protein

GRP78 is a major endoplasmic reticulum chaperone with Ca²⁺ binding ability. It can also act as an ER stress signal conditioner. GPR78 is associated with diseases such as schizophrenia. Upregulation of GRP78 expression is related to several cancer types, such as urinary, digestive, breast, brain, respiratory systems, and osteosarcoma. The presence of GRP78 autoantibodies in the serum of cancer patients is often associated with a poor prognosis because GRP78 promotes tumor cell proliferation, survival, and metastasis by inhibiting ER stress-induced apoptosis. It has been reported that overexpression of GRP78 is associated with chemoresistance. In addition, it has been reported that GRP78 inhibitor therapy or GRP78 knockdown may enhance chemotherapy-induced apoptosis in most of the cancer types mentioned above.

Fig.1 The GPR78 gene. (Underwood, 2006)

Application of GPR78 Membrane Protein in Literature

1. Xi J., et al. Suppression of GRP78 sensitizes human colorectal cancer cells to oxaliplatin by downregulation of CD24. Oncol Lett. 2018, 15(6): 9861-9867. PubMed ID: 29805687
   
   

   The article reveals that CD24 antagonizes L-OHP-induced cytotoxicity and that GRP78 is involved in this process. The combination of compounds that suppress GRP78 may help to improve the effectiveness of L-OHP in the treatment of colorectal cancer.

2. Wang X.Q., et al. Inhibition of 17beta-hydroxysteroid dehydrogenase type 7 modulates breast cancer protein profile and enhances apoptosis by down-regulating GRP78. J Steroid Biochem Mol Biol. 2017, 172: 188-197. PubMed ID: 28645527
   
   

   The article reports that down-regulation of GRP78 via 17β-HSD7 inhibition enhances cell apoptosis in response to Letrozole. The results suggest that inhibition of 17β-HSD7 would be a complementary strategy to Letrozole by suppression of GRP78 in ER+ breast cancer.

3. Dong D.D., et al. GPR78 promotes lung cancer cell migration and metastasis by activation of Gαq-Rho GTPase pathway. BMB Rep. 2016, 49(11): 623-628. PubMed ID: 27697106
   
   

   The results suggest that the knockdown of GPR78 inhibited lung cancer cell metastasis in vivo. GPR78 may be used as a novel regulator for lung cancer metastasis and may serve as a potential drug target against metastatic human lung cancer.

4. Stan R.C., et al. Human GRP78 affinity towards its signaling partners Ire1α and PERK is differently modulated by an unfolded protein client. Biochem Biophys Res Commun. 2017, 487(2): 375-380. PubMed ID: 28416388
   
   

   Authors in this group measured the binding affinities between human GRP78 and two transmembrane UPR sensors, with or without the addition of an unfolded protein client. It shows that human GRP78 affinity towards its signaling partners Ire1α and PERK is differently modulated by an unfolded protein client.

5. Ge Y., et al. The Protective Effect of Lacidipine on Myocardial Remodeling Is Mediated by the Suppression in Expression of GPR78 and CHOP in Rats. Evid Based Complement Alternat Med. 2015, 945076. PubMed ID: 25688281
   
   

   This article reveals that Lacidipine could lower blood pressure and prevent left ventricular hypertrophy accompanied by inhibiting expression of GRP78 and CHOP in ERS.

GPR78 Preparation Options

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Reference

1. Underwood S.L, et al. (2006). Association analysis of the chromosome 4p-located G protein-coupled receptor 78 (GPR78) gene in bipolar affective disorder and schizophrenia. Mol Psychiatry. 11(4): 384-94.

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