Initiation of proliferative events by human α‐thrombin requires both receptor binding and enzymic activity
Initiation of proliferative events by human α‐thrombin requires both receptor binding and enzymic activity
复制标题
人 α-凝血酶引发增殖事件需要受体结合和酶活性
DOI：
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复制
发表时间：
1984
影响因子：
4
通讯作者：
J. Fenton
中科院分区：
文献类型：
--
作者：
D. Carney;J. Stiernberg;J. Fenton
为了确定凝血酶高亲和力受体占有率和酶活性在凝血酶启动细胞增殖中的作用，我们使用了分离这些功能的凝血酶衍生物。我们之前的研究表明，酶活性的γ-凝血酶刺激离子流而不与高亲和力结合，而蛋白水解性抑制的DIP-α-凝血酶与高亲和力受体结合不能。由于这两种衍生物本身都不启动DNA合成，这表明完整的启动信号可能需要两个独立的事件序列。我们现在报道，DIP-α-凝血酶和γ-凝血酶的组合启动DNA合成和细胞增殖的水平接近天然α-凝血酶的最大启动水平。在与γ-凝血酶单独作用相同的浓度范围内，这种联合作用对α-凝血酶和DIP-α-凝血酶均具有剂量依赖性。因此，启动每一系列事件可能仅需要这些相同浓度的α-凝血酶。即使将衍生物单独加入，间隔长达8小时，也可以实现组合刺激。此外，任何一种衍生物的预孵育都缩短了天然α-凝血酶启动DNA合成的滞后时间。这些结果表明，受体占有率和酶活性都是凝血酶启动细胞增殖所必需的，并且每个动作都启动了一系列早期事件，使细胞向前进入增殖周期。
To determine the role of thrombin high‐affinity receptor occupancy and enzymic activity in thrombin initiation of cell proliferation, we have utilized thrombin derivatives which separate these functions. We previously showed that enzymically active γ‐thrombin stimulates ion fluxes without binding to high‐affinity sites, whereas proteolytically inhibited DIP‐α‐thrombin which binds to high‐affinity receptors does not. Since neither derivative initiates DNA synthesis by itself, this suggested that two separate sequences of events might be necessary for a complete initiation signal. We now report that the combination of DIP‐α‐thrombin and γ‐thrombin initiate DNA synthesis and cell proliferation to levels approaching the maximal initiation by native α‐thrombin. This combinatory effect is dose‐dependent for both γ‐thrombin and DIP‐α‐thrombin in the same concentration range as α‐thrombin alone. Thus, these same concentrations of α‐thrombin alone may be required to initiate each sequence of events. The combinatory stimulation could be achieved even if the derivatives were added individually up to 8 hr apart. Moreover, preincubation with either derivative shortened the lag period for initiation of DNA synthesis by native α‐thrombin. These results indicate that both receptor occupancy and enzymic activity are necessary for thrombin initiation of cell proliferation and that each action initiates a sequence of early events which moves the cell forward toward entry into a proliferative cycle.
鸡胚成纤维细胞的蛋白酶有丝分裂反应和人α-凝血酶的受体结合/加工。
DOI：
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发表时间：
1981
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Perdue,JF;Lubenskyi,W;Kivity,E;Sonder,SA;Fenton2nd,JW
通讯作者：
Fenton2nd,JW
有证据表明凝血酶对培养的人内皮细胞中花生四烯酸代谢的影响不是由高亲和力受体介导的。
DOI：
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发表时间：
1980
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Lollar,P;Owen,WG
通讯作者：
Owen,WG
DOI：
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发表时间：
1981
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Landis,BH;Koehler,KA;Fenton2nd,JW
通讯作者：
Fenton2nd,JW