Platelet signal transduction defect with G alpha subunit dysfunction and diminished G alpha(q) in a patient with abnormal platelet responses
Platelet signal transduction defect with G alpha subunit dysfunction and diminished G alpha(q) in a patient with abnormal platelet responses
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DOI：
10.1073/pnas.94.16.8750
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发表时间：
1997-08-05
影响因子：
11.1
通讯作者：
Rao, AK
中科院分区：
文献类型：
--
作者：
Gabbeta, J;Yang, X;Rao, AK
G蛋白在血小板活化的信号转导中起主要作用，我们以前曾报道过一例激动剂诱导的聚集、分泌、花生四烯酸释放和钙动员受损的患者，目前的研究表明，患者的血小板磷脂酶A(2)(胞浆和膜)活性正常，用抗体PAC-I通过流式细胞术检测到的糖蛋白(GP)IIb-IIa复合体的受体介导的激活作用减弱，尽管血小板上的GPIIb-IIIa的量正常。5‘-[γ-硫代]三磷酸鸟苷(GTP[伽马-S])诱导的血小板钙释放减少，提示存在激动剂受体远端缺陷，静息状态下血小板膜GTP酶活性(α-亚基的功能)正常，但在凝血酶、血小板激活因子或血栓素A(2)类似物U46619刺激下，与正常受试者相比减少。在基础状态和凝血酶刺激状态下，S-35标记的GTP与血小板膜的结合均减少，伊洛前列素(一种稳定的前列腺素I-2类似物)诱导的cAMP升高(由Gα(S)介导)和凝血酶抑制(由Gα(I)介导)正常，免疫印迹分析显示患者血小板膜Gα亚基减少(Q)(
G proteins play a major role in signal transduction upon platelet activation, We have previously reported a patient with impaired agonist-induced aggregation, secretion, arachidonate release, and Ca2+ mobilization, Present studies demonstrated that platelet phospholipase A(2) (cytosolic and membrane) activity in the patient was normal, Receptor-mediated activation of glycoprotein (GP) IIb-IIa complex measured by flow cytometry using antibody PAC-I was diminished despite normal amounts of GPIIb-IIIa on platelets. Ca2+ release induced by guanosine 5'-[gamma-thio]triphosphate (GTP[gamma S]) was diminished in the patient's platelets, suggesting a defect distal to agonist receptors, GTPase activity (a function of alpha-subunit) in platelet membranes was normal in resting state but was diminished compared with normal subjects on stimulation with thrombin, platelet-activating factor, or the thromboxane A(2) analog U46619. Binding of S-35-labeled GTP[gamma S] to platelet membranes was decreased under both basal and thrombin-stimulated states, Iloprost (a stable prostaglandin I-2 analog) -induced rise in cAMP (mediated by G alpha(s)) and its inhibition (mediated by G alpha(i)) by thrombin in the patient's platelet membranes were normal, Immunoblot analysis of G alpha subunits in the patient's platelet membranes showed a decrease in G alpha(q) (