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首页> 外文期刊>Life sciences >Serine/threonine phosphatases regulate platelet αiIbβ 3 integrin receptor outside-in signaling mechanisms and clot retraction
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Serine/threonine phosphatases regulate platelet αiIbβ 3 integrin receptor outside-in signaling mechanisms and clot retraction

机译：丝氨酸/苏氨酸磷酸酶调节血小板αiIbβ3整合素受体的外向内信号传导机制和血凝块收缩

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Aims We studied the role of serine/threonine phosphatases (PSTPs) on αIIbβ3 signaling and the potential selectivity of the level of PSTP inhibition with okadaic acid (OA) on α IIbβ3 signaling for regulation of platelet aggregation and clot retraction. Main methods We used washed platelets from normal donors and OA as inhibitor of PSTPs. Clot retraction was induced by 1 U/mL of thrombin. Reorganized cytoskeleton was isolated from Triton X-100 lysed platelets. The presence of proteins incorporated to the cytoskeleton was assayed by immunoblotting with specific antibodies. Key findings We found that both 100 and 500 nM OA blocked platelet mediated clot retraction. In contrast, only 500 nM OA inhibited thrombin-induced inside-out αIIbβ 3 activation, platelet aggregation, and cytoskeletal reorganization. Among markers of αIIbβ3 outside-in signaling, 500 nM OA inhibited the incorporation to the cytoskeleton of syk, src, and FAK (Focal Adhesion Kinase) tyrosine kinases and the incorporation and phosphorylation at Tyr759 of the β3 chain of αIIbβ3, while 100 nM OA only inhibited the FAK translocation and its tyrosine phosphorylation. Significance The level of inhibition of PSTPs by low or high OA concentration (33% and 73% inhibition, respectively) in intact whole cells differentially regulates platelet aggregation and integrin signaling, but have a common effect in blocking clot retraction. The latter may be associated with the presence of phosphorylated FAK in the cytoskeleton. This study reveals a novel target for anti-platelet treatment to block clot retraction without affecting the platelet hemostatic function by a partial inhibition of PSTPs.
机译：目的我们研究了丝氨酸/苏氨酸磷酸酶（PSTP）对αIIbβ3信号的作用以及冈比亚酸（OA）对αIIbβ3信号对PSTP抑制水平的潜在选择性，以调节血小板聚集和血凝块收缩。主要方法我们使用正常供体和OA的洗涤血小板作为PSTP的抑制剂。 1 U / mL凝血酶诱导凝块缩回。从Triton X-100裂解的血小板中分离出重组的细胞骨架。通过用特异性抗体免疫印迹分析掺入到细胞骨架中的蛋白质的存在。主要发现我们发现100和500 nM OA均可阻断血小板介导的血凝块收缩。相反，只有500 nM OA抑制凝血酶诱导的由内而外的αIIbβ3活化，血小板聚集和细胞骨架重组。在αIIbβ3内外信号的标志物中，500 nM OA抑制syk，src和FAK（Focal Adhesion Kinase）酪氨酸激酶在细胞骨架中的掺入以及αIIbβ3的β3链在Tyr759处的掺入和磷酸化，而100 nM OA仅抑制FAK易位及其酪氨酸磷酸化。意义完整全细胞中低或高OA浓度对PSTPs的抑制水平（分别为33％和73％抑制）差异性地调节血小板聚集和整联蛋白信号传导，但在阻止血块收缩方面具有共同作用。后者可能与细胞骨架中磷酸化FAK的存在有关。这项研究揭示了一种抗血小板治疗的新靶标，它可以通过部分抑制PSTP来阻止血块回缩而不影响血小板止血功能。

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