Introduction of P2RY10
P2RY10, also known as P2Y receptor family member 10, purinergic receptor P2Y, purinergic receptor P2Y10, P2Y-Like receptor, G-protein coupled purinergic receptor P2Y10, or LYPSR2, is a G-protein coupled receptor (GPCR) protein and has a molecular weight of 38.8 kDa. In humans, it is encoded by the gene P2RY10 which resides on the chromosome Xq21.1. And there exists a pseudogene for P2RY10 nearby on the chromosome X. This receptor is a member of the purine and pyrimidine nucleotide receptor family that is coupled to G proteins. Multiple alternatively spliced transcripts of P2RY10 gene have been observed. P2RY10 associated pathways are signaling by GPCR and peptide ligand-binding receptors.
|Basic Information of P2RY10|
|Protein Name||Putative P2Y purinoceptor 10|
|Aliases||P2Y10, P2Y-like receptor, LYPSR2|
|Organism||Homo sapiens (Human)|
Function of P2RY10 Membrane Protein
P2RY10 also belongs to the family of GPCR, preferentially activated by adenosine as well as uridine nucleotides. It acts as a receptor for lysophosphatidic acid and sphingosine-1-phosphate. P2RY10 activation leads to the mobilization of inositol 1,4,5-trisphosphate-sensitive Ca2+ storages, activation of inward plasma membrane currents, as well as stimulation of diacylglyceride-dependent protein kinases. It is demonstrated that this receptor is weakly present in blood leukocytes but nearly undetectable in undifferentiated cells and the following granulocytic differentiation. And P2RY10 can be upregulated during the promyelocytic cell differentiation along monocytic pathways. Additionally, P2RY10 is one of the highly upregulated genes at the late differentiation phage during in vitro eosinophilopoiesis. Furthermore, P2RY10, together with GPR34 and GPR174, is activated by lysophosphatidylserine (LysoPS), an endogenous lipid mediator. These three receptors are LysoPS-specific human GPCRs and constitute a LysoPS receptor family.
Fig.1 (A) Phylogenetic tree of the amino acid sequences of human P2Y family members. (Makide, 2014) (B) Expression of LysoPS receptors P2Y10 for LysoPS in PB leukocytes. (Hwang, 2018)
Application of P2RY10 Membrane Protein in Literature
The article discussed the human P2Y10 expression and function in cord blood (CB)-derived and peripheral blood (PB) eosinophils. LysoPS promoted eosinophil degranulation by P2Y10 and thus, P2Y10 was an attractive therapeutic target to control eosinophil-related diseases.
Recent report showed that three G protein-coupled receptors, LPS1/GPR34, LPS2/P2Y10, and LPS3/GPR174, are detected to react specifically with LysoPS, which raised the possibility that LysoPS exerting its roles by these receptors. Conclusively, LPS3 was expressed in many T cell subtypes and participated in the suppression of interleukin-2 production in CD4 T cells.
To elevate potency and receptor selectivity, LysoPS analogs with the conformational constraints of the glycerol moiety had been designed and synthesized. The reduced structural flexibility by fixation of the glycerol framework of LysoPS, and associated structures identified the compounds exhibiting high potency and selectivity for the activation of P2Y10 or GPR34.
There were two LysoPS-specific human G-protein-coupled receptors (GPCRs), P2Y10 (LPS2) and GPR174 (LPS3), recently had been identified by the ligand screening of orphan GPCRs. Herein, authors examined the structure-activity relationships of several synthetic LysoPS analogs toward above deorphanized LysoPS receptors.
This report currently found a GPCR for LPI (GPR55) and discovered three GPCRs for LysoPS including GPR34/LPS1, P2Y10/LPS2, and GPR174/LPS3. This review focused on these newly identified GPCRs and summarized actions of LPI and LysoPS as lipid mediators.
P2RY10 Preparation Options
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