Lysophosphatidic acid activates phosphoinositide 3-kinase and phospholipase C in human platelets: inhibitory effects of Wortmannin on phosphoinositide 3-kinase and aggregation.

Lysophosphatidic acid activates phosphoinositide 3-kinase and phospholipase C in human platelets: inhibitory effects of Wortmannin on phosphoinositide 3-kinase and aggregation.
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溶血磷脂酸激活人血小板中的磷酸肌醇 3-激酶和磷脂酶 C:渥曼青霉素对磷酸肌醇 3-激酶和聚集的抑制作用。

DOI:
10.1006/bbrc.1995.1839
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发表时间:
1995
期刊:
Biochemical and biophysical research communications.
影响因子:
--
通讯作者:
Rittenhouse,SE
Rittenhouse,SE
中科院分区:
--
文献类型:
--
作者:
Zhang,J;Rittenhouse,SE

文献摘要

被引文献

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溶血磷脂酸是一种具有生物活性的血清磷脂,已知具有生长因子样活性并引起血小板聚集。活化的磷酸肌醇3-激酶被认为参与细胞骨架重组和有丝分裂。我们报道溶血磷脂酸可激活血小板磷脂酰肌醇3-激酶,导致磷脂酰肌醇(3.4,5)P3和磷脂酰肌醇(3,4)P2的积累,并刺激磷脂酶C。Wortmannin是一种有效的磷酸肌醇3-激酶抑制剂,可阻断溶血磷脂酸诱导的血小板聚集,而不损害磷脂酶C的活化。作为一种纤维蛋白原与血小板整合素结合的拮抗剂,它能完全阻断血小板聚集,而不抑制磷酸肌醇3-激酶或磷脂酶C。我们认为,溶血磷脂酸,在激活磷脂酰肌醇3-激酶,促进血小板聚集,但血小板聚集反应溶血磷脂酸不显着增强磷脂酰肌醇3-激酶的激活。
Lysophosphatidic acid is a biologically active serum phospholipid known to have growth factor-like activities and to cause platelet aggregation. Activated phosphoinositide 3-kinase has been suggested to be involved in cytoskeletal reorganization and mitogenesis. We report that lysophosphatidic acid causes platelet phosphoinositide 3-kinase activation, leading to accumulation of phosphatidylinositol (3.4,5)P3and phosphatidylinositol (3,4)P2and stimulates phospholipase C. Wortmannin, a potent inhibitor of phosphoinositide 3-kinase, blocks platelet aggregation induced by lysophosphatidic acid without impairing phospholipase C activation. Eristostatin, an antagonist of fibrinogen binding to platelet integrin, completely blocks platelet aggregation without inhibiting phosphoinositide 3-kinase or phospholipase C. We suggest that lysophosphatidic acid, in activating phosphoinositide 3-kinase, promotes platelet aggregation, but that platelet aggregation in response to lysophosphatidic acid does not significantly enhance phosphoinositide 3-kinase activation.