NPY5R Membrane Protein Introduction

Introduction of NPY5R

Neuropeptide Y receptor 5 (NPY5R), a receptor neuropeptide Y and peptide YY, is a protein that in humans is encoded by the NPY5R gene. As a member of the Neuropeptide Y receptor family, it also belongs to the G-protein-coupled receptor superfamily. NPY receptor family comprises four functional NPY receptor subtypes (Y1R, Y2R, Y4R Y5R), it exerts a variety of physiological processes in humans via four different receptor subtypes. NPY5R is involved in a pathway that protects neuroblastoma cells from chemotherapy-induced cell death, providing a possible therapeutic target against neuroblastoma. Three transcript variants encoding the same protein have been found for this gene. It also responds to pancreatic polypeptide (PP).

Function of NPY5R Membrane Protein

As we all know overexpression of neuropeptide Y (NPY) and its receptor system has been reported in various types of cancers. Similar to Y2R, human NPY5R can be activated by NPY, PYY, NPY3-36, and PYY 3-36. NPY5R has been implicated in cell growth and angiogenesis. And some studies have shown that NPY5R plays an important role in the hypothalamic regulation of feeding. In addition, the previous studies showed that NPY5R is the primary NPY receptor subtype in mouse cardiac myocytes and its activation leads to increased PKC activity and to mitogen-activated protein kinase phosphorylation and activity. These signaling pathways have been implicated in NPY induced cardiac hypertrophy through NPY5R activation.

Fig.1 Structure of NPY5R membrane protein.

Application of NPY5R Membrane Protein in Literature

1. Czarnecka M., et al. Neuropeptide Y receptor Y5 as an inducible pro-survival factor in neuroblastoma: implications for tumor chemoresistance. Oncogene. 2015, 34(24): 3131-43. PubMed ID: 25132261.
   
   

   This article showed that in Neuroblastoma (NB) cells, Brain-derived neurotrophic factor (BDNF) stimulates the synthesis of NPY and induces expression of another one of its receptors, NPY5R. And the NPY/Y5R pathway may become a novel therapeutic target for patients with refractory NB, thus far an incurable form of this disease.

2. Sheriff S., et al. Neuropeptide Y Y5 receptor promotes cell growth through extracellular signal-regulated kinase signaling and cyclic AMP inhibition in a human breast cancer cell line. Molecular cancer research. 2010, 8(4): 604-14. PubMed ID: 20332211.
   
   

   This article identified the role of NPY5R in breast cancer, so they screened several breast cancer cell lines to examine the expression of NPY5R and its function in breast cancer. Their results suggested that NPY5R plays an important role in cancer cell growth and migration and could be a novel therapeutic target for breast cancer.

3. Beauverger P., et al. Functional characterization of human neuropeptide Y receptor subtype five specific antagonists using a luciferase reporter gene assay. Cellular signaling. 2005, 17(4): 489-96. PubMed ID: 15601626.
   
   

   The author of this group established a method for the functional study of new ligands to obtain a stable cell line expressing that this recombinant receptor has impaired the development of tools necessary to establish its molecular pharmacology. Finally, they showed a series of potent nonpeptidic antagonists (affinity >10(-9) M) that form a new class of active NPY5R antagonists.

4. Rodriguez M., et al. Molecular identification of the long isoform of the human neuropeptide Y Y5 receptor and pharmacological comparison with the short Y5 receptor isoform. The Biochemical journal. 2003, 369 (Pt 3): 667-73. PubMed ID: 12398768.
   
   

   This article showed Y5(L) mRNA differs from Y5(S) mRNA in its 5' end, generating a putative open reading frame with 30 additional nucleotides upstream of the initiator AUG compared with the Y5(S) mRNA. Finally, they have shown that the two AUG triplets contained in the 5' untranslated region of Y5(L) mRNA did not affect receptor expression.

5. Medeiros P.J., et al. Neuropeptide Y Y5-receptor activation on breast cancer cells acts as a paracrine system that stimulates VEGF expression and secretion to promote angiogenesis. Peptides. 2013, 48: 106-13. PubMed ID: 23932937.
   
   

   The authors of this group using selective NPY Y-receptor agonists (Y1R, Y2R, and Y5R) observed an increase in VEGF expression only when cells were treated with NPY5R agonist. Their data highlight a novel mechanism by which NPY may promote breast cancer progression, and further implicate a pathological role of the NPY5R.

NPY5R Preparation Options

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