Calcium oscillation and phosphatidylinositol 3-kinase positively regulate integrin αIIbβ3-mediated outside-in signaling

Der Shan Sun, Szecheng J. Lo, Chi Hung Lin, Mei Shiuan Yu, Ching Yi Huang, Yao Fong Chen, Hsin Hou Chang*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

19 Scopus citations


The frequency of calcium oscillation reveals the platelet activation status, however, the biological significance of the periodic calcium responses and methods of communication with other integrin-mediated signals are not clear. RGD-containing disintegrin rhodostomin coated substrates were employed to enhance platelet spreading and calcium oscillation through direct binding and clustering of the receptor integrin αIIbβ3. The results showed that the activation of phosphatidylinositol 3-kinase (PI3-K) and internal calcium pathways were crucial for αIIbβ 3 outside-in signaling. PI3-K antagonists wortmannin and LY294002 inhibited disintegrin substrates and induced platelet spreading and calcium oscillation. At the same time, pretreatment of platelets with the microsomal calcium-ATPase inhibitor thapsigargin to deplete internal calcium stores severely impaired the calcium oscillation as well as PI3-K activation and spreading on disintegrin substrates. Because inhibition of one pathway could inhibit the other, our data indicates that PI3-K and calcium oscillation are synergistically operated and form a positive-feedback regulation in integrin αIIbβ3-mediated outside-in signaling.

Original languageEnglish
Pages (from-to)321-333
Number of pages13
JournalJournal of Biomedical Science
Issue number2
StatePublished - 03 2005


  • Calcium oscillation
  • Integrin outside-in signaling
  • Integrin αβ
  • Phosphatidylinositol 3-kinase


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