JBC：凝血的新调控机制

2012年11月23日 --近日，乔治·华盛顿大学医学及健康科学（SMHS）中研究人员在是在Journal of Biological Chemistry杂志上发表新论文证实了血液凝血级联反应存在新的调节机制。

论文题目为p21-activated Kinase-1 Signaling Regulates Transcription of Tissue Factor and Tissue Factor Pathway Inhibitor，该研究突破性的发现一个新的监管机构调控凝血级联。

许多人都知道划伤或损伤后血液会凝固，血液凝血是一个持续的过程，是一个动态过程。凝血由组织因子（TF）调控和启动。TF与许多其他蛋白质创建了凝固一系列连锁反应。TF的活动积极调节凝血，而组织因子途径抑制物（TFPI）是一个负调节控制因子，两者之间创造了一个平衡状态。

Sánchez-Solana说：新研究首次发现PAK1（p21活化激酶1）与TF，TFPI的表达有关联。研究者指出，PAK1能够诱导TF的表达，但同时也抑制TFPI的表达，引发一个过度凝血状态。认识这一点这不仅对了解凝血很重要，同时也对探究许多癌症等疾病有帮助。通过控制PAK1的表达或活性，可以用来控制凝血过程。

Kumar说：如果这些结果能在动物模型中得到验证，那么我们的研究就可以证实干扰PAK1信号影响凝血过程是可行的。

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p21-activated Kinase-1 Signaling Regulates Transcription of Tissue Factor and Tissue Factor Pathway Inhibitor

Tissue factor (TF) is a cell-surface glycoprotein responsible for initiating the coagulation cascade. Besides its role in homeostasis, studies have shown the implication of TF in embryonic development, cancer-related events, and inflammation via coagulation-dependent and -independent (signaling) mechanisms. Tissue factor pathway inhibitor (TFPI) plays an important role in regulating TF-initiated blood coagulation. Therefore, transcriptional regulation of TF expression and its physiological inhibitor TFPI would allow us to understand the critical step that controls many different processes. From a gene profiling study aimed at identifying differentially regulated genes between wild-type (WT) and p21-activated kinase 1-null (PAK1-KO) mouse embryonic fibroblasts (MEFs), we found TF and TFPI are differentially expressed in the PAK1-KO MEFs in comparison with wild-type MEFs. Based on these findings, we further investigated in this study the transcriptional regulation of TF and TFPI by PAK1, a serine/threonine kinase. We found that the PAK1·c-Jun complex stimulates the transcription of TF and consequently its procoagulant activity. Moreover, PAK1 negatively regulates the expression of TFPI and additionally contributes to increased TF activity. For the first time, this study implicates PAK1 in coagulation processes, through its dual transcriptional regulation of TF and its inhibitor.