Pin1 induces the ADP-induced migration of human dental pulp cells through P2Y1 stabilization
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Soo-A Kim1, Hong Seok Choi2, Sang-Gun Ahn3
1Department of Biochemistry, College of Oriental Medicine, Dongguk University, Gyeongju, South Korea
2College of Pharmacy, Chosun University, Gwangju, Republic of Korea
3Department of Pathology, School of Dentistry, Chosun University, Gwangju, Republic of Korea
Sang-Gun Ahn, email: [email protected]
Keywords: Pin1, P2Y1, MAPKs, human dental pulp cells, cell migration
Received: August 16, 2016 Accepted: October 28, 2016 Published: November 16, 2016
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.
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