P2RY2

Official Full Name

purinergic receptor P2Y2

Organism

Homo sapiens

GeneID

5029

Background

The product of this gene belongs to the family of P2 receptors, which is activated by extracellular nucleotides and subdivided into P2X ligand-gated ion channels and P2Y G-protein coupled receptors. This family has several receptor subtypes with different pharmacological selectivity, which overlaps in some cases, for various adenosine and uridine nucleotides. This receptor, found on many cell types, is activated by ATP and UTP and is reported to be overexpressed on some cancer cell types. It is involved in many cellular functions, such as proliferation, apoptosis and inflammation. Three transcript variants encoding the same protein have been identified for this gene. [provided by RefSeq, Mar 2013]

Synonyms

P2U; HP2U; P2U1; P2UR; P2Y2; P2RU1; P2Y2R;

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Detailed Information

Cross-talk between the P2RY2 receptor and epidermal growth factor receptor induce carcinoma cell migration

In developed countries, among the gynecological diseases, epithelial ovarian cancer patients have the highest mortality rate. Elevation of their mortality is accompanied with dissemination of tumor cells throughout the peritoneal cavity and occurrence of the secondary tumors in various organs. Thus, the identification of pathways regulating the cell invasiveness is critical of understanding the lethality implicated mechanisms of this disease. In response to various stimuli, ATP is released from Cells, and this behavior plays a pivotal role in mediating autocrine and paracrine signaling events. There is mounting evidence showing that metabolic deregulation induced by cancer cells leads to an increase in ATP production. The fluctuation of the ATP level is enough to activate P2 receptors, more than this, other nucleotides can activate two families of purinergic receptors, named as P2RX and P2RY receptors. P2RY, a G protein-coupled receptor (GPCR), can be activated by purines and pyrimidines for signaling cascade through different second messengers depending on the heterotrimeric G protein associated with them. Human P2RY2 receptor can be activated ATP and UTP at the similar potency with purines or pyrimidines.

In physiological and pathophysiological processes, many studies have demonstrated the participation of the P2RY2 receptor in inducing migration or EMT process and transactivation of the epidermal growth factor receptor (EGFR) is important for this migration. The activator of the EGFR (a family of membrane receptors with intrinsic tyrosine kinase activity), epidermal growth factor (EGF) has been proven to be a participant in the EGF-EGFR-mediated signaling in the progression and invasiveness of different types of carcinomas. Involvement of EGFR activation induced migratory phenotype in the EMT process was observed in ovarian carcinoma cells. And EGFR activity in ovarian carcinoma-derived cells has also been found to be related with proliferation regulation. Trans-activation of EGFR by other receptors is a well-established phenomenon in cancer models. With specialty in ovarian carcinoma, EGFR has been demonstrated to be transactivated by the chemokine CXCL1 and the membrane estrogen receptor GPER1.

Cerebral Ischemia can be alleviated by P2RY2 mediated YAP phosphorylation inhibition and mitochondrial fission reduction

It has been well known that P2RY2 has involvement in the regulation of cell proliferation and apoptosis. In the established models, included middle cerebral artery occlusion (MCAO) model in rats and oxygen-glucose deprivation (OGD) model in PC12 cells, expressions level of the P2RY2 was up-regulated, while SOD activity and myocytic and mitochondrial fusion factors were down-regulated, and overexpression of P2RY2 could reverse this phenomenon. P2RY2 expression up-regulation induced Yes-associated protein (YAP) phosphorylation or some other promotions of the nuclear translocation of YAP can inhibit cell apoptosis, and it can be reversed by YAP inhibitor verteporfin.

Figure 1. Involvement of P2RY2 in the regulation of cell proliferation and apoptosis. (Long-xing xue, et al. 2021)

References:

Martínez‐Ramírez A S, et al. The P2RY2 receptor induces carcinoma cell migration and EMT through cross‐talk with epidermal growth factor receptor. Journal of cellular biochemistry, 2016, 117(4): 1016-1026.
Xue L, et al. P2RY2 alleviates cerebral ischemia-reperfusion injury by inhibiting YAP phosphorylation and reducing mitochondrial fission. Neuroscience, 2021.

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