GPR182 Membrane Protein Introduction

Introduction of GPR182

GPR182, formerly known as adrenomedullin receptor ADMR, is a member of “Class A” G-protein coupled receptor (GPCR) family, which can mediate cellular signal transduction and thereby involved in multiple biological processes. GPCRs represent prospective targets for pharmacological treatment, based on their physiological relevance. The predicted structure of GPR182 has an extracellular N terminus, seven transmembrane helices and an intracellular C terminus, typical structure of GPCRs. The third transmembrane helix is considered as the G protein binding domain.

Function of GPR182 Membrane Protein

Beneficial from Northern Blot analysis, GPR182 was reported to be expressed in numerous regions, such as heart, immune system, skeletal muscle, adrenal gland, and liver. The wide distribution suggests multiple functions in physiological processes. Furthermore, GPR182 is expressed in intestinal stem cells (ISCs) as a negative regulator of proliferation during regeneration and adenoma formation by inhibiting ERK signaling. GPR182 are also found in vascular endothelial cells of zebrafish embryos and developing mouse endothelial cells. Controversially, GPR182 was previously cloned as a putative receptor for the multifunctional peptide adrenomedullin (ADM), which is consistent with the xenograft tumor growth. It is demonstrated that GPR182 can regulate endothelial subtype-specific sinusoidal differentiation and sinusoidal functions through ERK and SRF pathways. With the atypical chemokine receptor 3 (ACKR3) as its closest paralog, GPR182 is geared to the subgroup of chemokine receptors family by phylogeny.

Fig.1 Structure of GPR182 membrane protein.

Application of GPR182 Membrane Protein in Literature

1. Schmid C.D., et al. GPR182 is a novel marker for sinusoidal endothelial differentiation with distinct GPCR signaling activity in vitro. Biochemical and biophysical research communications. 2018, 497(1): 32-38. PubMed ID: 29408502
   
   

   The authors reveal that GPR182 is expressed in liver sinusoidal endothelial cells (LSEC) and endothelial cells (EC) in healthy human tissues. They identified GPR182 is a potential LSEC-specific GPCR, which can regulate the downstream signaling via ERK and SRF pathways. So it may be involved in regulating endothelial subtype-specific sinusoidal differentiation and sinusoidal functions.

2. Kechele D.O., et al. Orphan Gpr182 suppresses ERK-mediated intestinal proliferation during regeneration and adenoma formation. The Journal of clinical investigation. 2017, 127(2): 593-607. PubMed ID: 28094771
   
   

   Aided by a genetically engineered knockin reporter mouse, the authors map the expression pattern of the GPR182 during development and adulthood. They implicate GPR182 may be a negative regulator of intestinal MAPK signaling-induced proliferation, particularly during regeneration and adenoma formation.

3. Xu M., et al. Adrenomedullin promotes the growth of pancreatic ductal adenocarcinoma through recruitment of myelomonocytic cells. Oncotarget. 2016, 7(34): 55043. PubMed ID: 25061099
   
   

   This article figures out ADM can enhance the migration and invasion of myelomonocytic cells through activation of the MAPK, PI3K/Akt and eNOS signaling pathways. ADM knockdown can significantly impede the recruitment of myelomonocytic cells and tumor angiogenesis. GPR182 is thought to be ADM receptor and involves in the bioprocess.

4. Ramachandran V., et al. The ADMR receptor mediates the effects of adrenomedullin on pancreatic cancer cells and on cells of the tumor microenvironment. PLoS One. 2009, 4(10): e7502. PubMed ID: 19847298
   
   

   This article shows that ADMR can mediate the stimulatory effects of adrenomedullin on cancer cells, endothelial and stellate cells in the tumor microenvironment. Silencing of ADMR strongly reduces tumor development.

5. Dötsch J., et al. Nitric oxide increases adrenomedullin receptor function in rat mesangial cells. Kidney international. 2002, 61(5): 1707-1713. PubMed ID: 11967020
   
   

   The authors highlight that nitric oxide (NO) increases adrenomedullin receptor function in rat mesangial cells. The enhancement of ADM signal transduction is performed by cGMP dependent pathway.

GPR182 Preparation Options

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