Activation of alphaVbeta3 on vascular cells controls recognition of prothrombin.
Activation of alphaVbeta3 on vascular cells controls recognition of prothrombin.
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DOI：
10.1083/jcb.143.7.2081
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发表时间：
1998-12-28
期刊：
影响因子：
--
通讯作者：
Plow EF
中科院分区：
文献类型：
--
作者：
Byzova TV;Plow EF
血管稳态的调节依赖于血管壁细胞和凝血系统之间的协作。证明了内皮细胞和平滑肌细胞上的整合素αVβ3与凝血系统的关键酶原凝血酶原之间的直接相互作用，并且整合素的活化是受体接合所必需的。凝血酶原是这些细胞上αVβ3的配体的证据包括：（a）凝血酶原通过RGD识别特异性与纯化的αVβ3结合;（B）凝血酶原支持αVβ3介导的受刺激内皮细胞和平滑肌细胞的粘附;（c）悬浮液和单层内皮细胞通过αVβ3识别可溶性凝血酶原。αVβ3介导的细胞与凝血酶原的粘附，而不是与纤维蛋白原的粘附，需要受体的激活。因此，αVβ3受体的功能是配体定义的，凝血酶原和纤维蛋白原代表活化依赖性和活化非依赖性配体。αVβ3的激活不仅可被模型激动剂PMA和Mn ~（2+）所诱导，也可被生理上相关的激动剂ADP所诱导。蛋白激酶C和钙蛋白酶的抑制阻止了血管细胞上αVβ3的激活，表明这些分子参与了激活整合素的由内而外的信号传导事件。αVβ3与凝血酶原相互作用的能力可能在维持止血中发挥重要作用;在一般水平上，αVβ3的配体选择可能受该整合素的活化状态控制。
Regulation of vascular homeostasis depends upon collaboration between cells of the vessel wall and blood coagulation system. A direct interaction between integrin αVβ3 on endothelial cells and smooth muscle cells and prothrombin, the pivotal proenzyme of the blood coagulation system, is demonstrated and activation of the integrin is required for receptor engagement. Evidence that prothrombin is a ligand for αVβ3 on these cells include: (a) prothrombin binds to purified αVβ3 via a RGD recognition specificity; (b) prothrombin supports αVβ3-mediated adhesion of stimulated endothelial cells and smooth muscle cells; and (c) endothelial cells, either in suspension and in a monolayer, recognize soluble prothrombin via αVβ3. αVβ3-mediated cell adhesion to prothrombin, but not to fibrinogen, required activation of the receptor. Thus, the functionality of the αVβ3 receptor is ligand defined, and prothrombin and fibrinogen represent activation- dependent and activation-independent ligands. Activation of αVβ3 could be induced not only by model agonists, PMA and Mn2+, but also by a physiologically relevant agonist, ADP. Inhibition of protein kinase C and calpain prevented activation of αVβ3 on vascular cells, suggesting that these molecules are involved in the inside-out signaling events that activate the integrin. The capacity of αVβ3 to interact with prothrombin may play a significant role in the maintenance of hemostasis; and, at a general level, ligand selection by αVβ3 may be controlled by the activation state of this integrin.
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影响因子：
7.8
作者：
BARSHAVIT, R;ESKOHJIDO, Y;VLODAVSKY, I
通讯作者：
VLODAVSKY, I
DOI：
10.1073/pnas.84.18.6471
发表时间：
1987-09-01
影响因子：
11.1
作者：
CHERESH, DA
通讯作者：
CHERESH, DA
影响因子：
20.3
作者：
Bombeli, T;Karsan, A;Harlan, JM
通讯作者：
Harlan, JM
影响因子：
7.8
作者：
BARSHAVIT, R;SABBAH, V;DEJANA, E
通讯作者：
DEJANA, E
影响因子：
7.5
作者：
Habermann, Brunhilde Felding;Cheresh, David A.
通讯作者：
Cheresh, David A.