The P2Y12 receptor induces platelet aggregation through weak activation of the αIIbβ3 integrin – a phosphoinositide 3‐kinase‐dependent mechanism
- 28 August 2001
- journal article
- Published by Wiley in FEBS Letters
- Vol. 505 (2), 281-290
- https://doi.org/10.1016/s0014-5793(01)02824-1
Abstract
High concentrations of adenosine‐5′‐diphosphate ADP are able to induce partial aggregation without shape change of P2Y1 receptor‐deficient mouse platelets through activation of the P2Y12 receptor. In the present work we studied the transduction pathways selectively involved in this phenomenon. Flow cytometric analyses using R‐phycoerythrin‐conjugated JON/A antibody (JON/A‐PE), an antibody which recognizes activated mouse αIIbβ3 integrin, revealed a low level activation of αIIbβ3 in P2Y1 receptor‐deficient platelets in response to 100 μM ADP or 1 μM 2MeS‐ADP. Adrenaline induced no such activation but strongly potentiated the effect of ADP in a dose‐dependent manner. Global phosphorylation of 32P‐labeled platelets showed that P2Y12‐mediated aggregation was not accompanied by an increase in the phosphorylation of myosin light chain (P20) or pleckstrin (P47) and was not affected by the protein kinase C (PKC) inhibitor staurosporine. On the other hand, two unrelated phosphoinositide 3‐kinase inhibitors, wortmannin and LY294002, inhibited this aggregation. Our results indicate that (i) the P2Y12 receptor is able to trigger a P2Y1 receptor‐independent inside‐out signal leading to αIIbβ3 integrin activation and platelet aggregation, (ii) ADP and adrenaline use different signaling pathways which synergize to activate the αIIbβ3 integrin, and (iii) the transduction pathway triggered by the P2Y12 receptor is independent of PKC but dependent on phosphoinositide 3‐kinase.This publication has 25 references indexed in Scilit:
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