title: Pin1 induces the ADP-induced migration of human dental pulp cells through P2Y1 stabilization.
abstract: PIN1, which belongs to a family of prolyl isomerases, specifically binds to phosphorylated Ser/Thr-pro motifs to catalytically regulate the post-phosphorylation conformation of its substrates. This study aimed to investigate the importance of Pin1 expression in human dental pulp cells (hDPCs) to understand the involvement of Pin1 in the regulation of P2Y1 and the activation of ADP-mediated P2Y1 signaling. This study found that the protein levels of P2Y1 gradually decreased after the onset of cell recovery following heat stress. Interestedly, hDPC migration significantly decreased during the recovery period. An in vitro study revealed that the silencing of PIN1 by siRNA or the pharmacologic inhibition of its activity decreased the migration of P2Y1 and P2Y1 expression in these cells. In addition, we found that Pin1 directly interacts with S252 of P2Y1 and that its binding stabilizes the P2Y1 protein to increase migration activity. These results strongly suggest that Pin1 mediates cell migration by stabilizing P2Y1 and that the Pin1/P2Y1 signaling pathways might serve as a novel mechanism of cell migration progression in hDPCs.
authors.affiliation: Department of Biochemistry, College of Oriental Medicine, Dongguk University, Gyeongju, South Korea.
authors.forename: Soo-A
authors.initials: SA
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Chosun University, Gwangju, Republic of Korea.
authors.forename: Hong Seok
authors.initials: HS
authors.lastname: Choi
authors.affiliation: Department of Pathology, School of Dentistry, Chosun University, Gwangju, Republic of Korea.
authors.forename: Sang-Gun
authors.initials: SG
authors.lastname: Ahn
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003782:Dental Pulp / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D018869:Heat-Shock Response; D006801:Humans; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D000072340:NIMA-Interacting Peptidylprolyl Isomerase / Q000235:genetics / Q000378:metabolism*; D055550:Protein Stability; D058912:Purinergic P2Y Receptor Agonists / Q000494:pharmacology*; D034622:RNA Interference; D058472:Receptors, Purinergic P2Y1 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection
chemical_list: D000072340:NIMA-Interacting Peptidylprolyl Isomerase; C546382:P2RY1 protein, human; D058912:Purinergic P2Y Receptor Agonists; D058472:Receptors, Purinergic P2Y1; D000244:Adenosine Diphosphate; D020928:Mitogen-Activated Protein Kinases; C000606846:PIN1 protein, human; C000606850:Pin1 protein, mouse
keywords: MAPKs; P2Y1; Pin1; cell migration; human dental pulp cells