Sorisky A, King W G, Rittenhouse S E
Department of Biochemistry, University of Vermont College of Medicine, Burlington 05405.
Biochem J. 1992 Sep 1;286 ( Pt 2)(Pt 2):581-4. doi: 10.1042/bj2860581.
Differences in regulation of the accumulation of PtdIns(3,4)P2 versus that of PtdIns(3,4,5)P3 were noted in thrombin-stimulated human platelets. The rapid (within 20 s) response of PtdIns(3,4,5)P3 contrasted with a distinct lag in the accumulation of PtdIns(3,4)P2 that was followed by a pronounced increase by 90 s. The presence of 2.5 mM-CaCl2 further elevated PtdIns(3,4)P2 by 50-120%, but only at a late stage (after 90 s). Tetrapeptide RGDS (Arg-Gly-Asp-Ser), which blocks the interaction of ligands such as fibrinogen with platelet integrin alpha IIb beta 3 (GPIIb-IIIa), inhibited only the late-phase PtdIns(3,4)P2 accumulation that was associated with added Ca2+. Although stimulated tyrosine phosphorylation of platelet protein (total cell lysate) was altered by Ca2+ or RGDS, we could not identify any such proteins that were affected comparably to PtdIns(3,4)P2. In contrast to the PtdIns(3,4)P2 response, the accumulation of PtdIns(3,4,5)P3 was unaffected by Ca2+ or RGDS at any time.
在凝血酶刺激的人血小板中，已观察到磷脂酰肌醇-3,4-二磷酸（PtdIns(3,4)P2）与磷脂酰肌醇-3,4,5-三磷酸（PtdIns(3,4,5)P3）积累调控方面的差异。PtdIns(3,4,5)P3的快速（20秒内）反应与PtdIns(3,4)P2积累的明显延迟形成对比，后者在90秒后显著增加。2.5 mM氯化钙的存在使PtdIns(3,4)P2在后期（90秒后）进一步升高50 - 120%。四肽RGDS（精氨酸-甘氨酸-天冬氨酸-丝氨酸）可阻断纤维蛋白原等配体与血小板整合素αIIbβ3（糖蛋白IIb-IIIa）的相互作用，它仅抑制与添加钙离子相关的后期PtdIns(3,4)P2积累。尽管钙离子或RGDS改变了血小板蛋白（全细胞裂解物）的酪氨酸磷酸化刺激水平，但我们未能鉴定出任何与PtdIns(3,4)P2受影响程度相当的此类蛋白质。与PtdIns(3,4)P2反应不同，PtdIns(3,4,5)P3的积累在任何时候都不受钙离子或RGDS的影响。
