PI3-kinase is essential for ADP-stimulated integrin α IIbβ3-mediated platelet calcium oscillation, implications for P2Y receptor pathways in integrin αIIbβ 3-initiated signaling cross-talks

Der Shan Sun, Szecheng J. Lo, Wei Jern Tsai, Chi Hung Lin, Mei Shiuan Yu, Yao Fong Chen, Hsin Hou Chang*

*Corresponding author for this work

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Phosphatidylinositol 3-kinase (PI3K) pathway is important for platelet activation. Recent studies showed that PI3K and oscillative calcium could cross talk to each other and positively regulate integrin α IIbβ 3-mediated outside-in signaling. However, the mechanism of this feedback regulation remains to be further characterized. Here we found that treatments of both PI3K inhibitor wortmannin and P2Y1 inhibitor A3P5P could inhibit granular secretion in platelets. Additionally, when RGD-substrate adherent platelets were treated with the ADP scavenger apyrase to deplete the granular-released ADP, their attachments in engaging with substrates became looser and the frequency of calcium oscillation decreased. Since it is known that ADP stimulates the PI3K and calcium signal primarily through P2Y12 and P2Y1 receptors respectively, our data indicated that integrin α IIbβ3 downstream PI3K and calcium activation might be not completely coupled to integrin associated signaling complex, but in part through feedback stimulation by granular released ADP. Our data indicates the important roles of PI3K and granular released ADP in coordinating the feedback regulations in integrin αIIbβ3-mediated platelet activation.

Original languageEnglish
Pages (from-to)937-948
Number of pages12
JournalJournal of Biomedical Science
Volume12
Issue number6
DOIs
StatePublished - Dec 2005

Keywords

  • ADP
  • Calcium oscillation
  • Integrin αβ
  • P2Y receptors
  • Phosphatidylinositol 3-kinase

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