The Role of Thrombin and Thrombin Receptor Activating Peptide (TRAP-508) in Initiation of Tissue Repair
The Role of Thrombin and Thrombin Receptor Activating Peptide (TRAP-508) in Initiation of Tissue Repair
复制标题
凝血酶和凝血酶受体激活肽 (TRAP-508) 在启动组织修复中的作用
作者：
J. Stiernberg;W. Redin;W. Scott Warner;D. Carney
凝血酶是众所周知的纤维蛋白凝块形成和血小板激活的关键酶，但它作为生长刺激剂和凝血后细胞效应的启动者的核心作用才刚刚开始被认识到[1]。这可能解释了为什么在伤口愈合的潜在治疗增强剂名单中，它在很大程度上被忽视了。由于凝血酶是一种蛋白酶，其刺激细胞增殖的机制一直难以理解。早期的研究表明，凝血酶的有丝分裂活性不是简单的蛋白分解的结果，因为包括糜蛋白酶在内的其他丝氨酸蛋白酶不能有丝分裂[2]。相反，似乎在成纤维细胞和其他细胞上有一种特殊的高亲和力凝血酶受体(3)。这些受体已被标记(4)，显示(5，6)，并分离(7，S)。完整的回顾见(9)或(1，LO)。大量研究表明，凝血酶有丝分裂需要两种受体介导的信号。一种是由蛋白水解性凝血酶启动的，涉及刺激肌醇磷脂的周转(11)。蛋白激酶C的激活(12)，NaCIH+反向端口的刺激(13)，CFos和c-rnyc的诱导(14)；第二个涉及非蛋白水解性高亲和力受体占据所产生的信号(15)。这些后来的高亲和力相互作用刺激了cAMP(16)的瞬时增加，以及一组额外的尚未定义的信号。最近从人巨核细胞的mRNA(17)、仓鼠成纤维细胞(IS)和大鼠的平滑肌细胞(19)中克隆了一种“功能”的凝血酶受体成分(G蛋白连接受体家族)。该受体被一种独特的蛋白水解性切割激活，该切割暴露出一种能够自我激活该受体成分(17)的G蛋白连接功能的系链配体。因此，这种受体现在被称为蛋白水解型凝血酶受体(部分)。似乎所有由蛋白水解性凝血酶激活的G蛋白相关信号都是通过该组分的裂解而启动的。然而，如上所述，凝血酶有丝分裂所需的一些信号需要高亲和力的受体占据，但不需要蛋白分解。此外，最近的研究表明，仅通过拴系配基多肽激活部分不能刺激许多细胞的有丝分裂(20和Carney，未发表)。因此，与“双信号”假说相一致
Thrombin is well known as the pivotal enzyme in the formation of fibrin clots and platelet activation, but is just beginning to be recognized for its central role as a growth stimulator and initiator of postclotting cellular effects (1). This may explain why it has largely been overlooked in lists of potential therapeutic enhancers of wound healing. Because thrombin is a protease, its mechanism for stimulating cell proliferation has been difficult to understand. Early studies showed that thrombin's mitogenic activity was not simply the result of proteolysis, since other serine proteases including chymotrypsin were not mitogenic (2). Instead, it appeared that there was a specific high-affinity receptor for thrombin on fibroblasts and other cells (3). These receptors have been labeled (4), visualized (5,6), and isolated (7,s). For complete review see (9) or (1,lO). A number of studies have shown that thrombin mitogenesis requires two types of receptor mediated signals. One, initiated by proteolytically active thrombin, involves stimulation of phosphoinositide turnover (11). activation of protein kinase C (12), stimulation of NaCIH+ antiport (13), and induction of cfos and c-rnyc (14); a second involves signals generated by non-proteolytic high-affinity receptor occupancy (15). These later high-affinity interactions stimulate a transient increase in CAMP (16), and an additional set of yet to be defined signals. A "functional" thrombin receptor component (of the G protein-linked receptor family) has been recently cloned from human megakaryocyte mRNA (17), hamster fibroblasts (IS), and rat smooth muscle cells (19). This receptor is activated by a unique proteolytic cleavage which exposes a tethered ligand capable of self-activating the G protein-linked functions of this receptor component (17). This receptor is thus now referred to as the proteolytically-activated receptor for thrombin (PART). It appears that all of the G protein-linked signals stimulated by proteolytically active thrombin are initiated through the cleavage of this component. As described above, however, some of the signals required for thrombin mitogenesis require high-affinity receptor occupancy, but not proteolysis. In addition, recent studies have shown that activation of PART by the tethered ligand peptide alone cannot stimulate mitogenesis in many cells (20 and Carney, unpublished). Thus, consistent with the "double signal" hypothesis
影响因子：
56.9
作者：
BEVILACQUA, MP;STENGELIN, S;SEED, B
通讯作者：
SEED, B
在佛波醇肉豆蔻醋酸酯存在的情况下，凝血酶受体占据启动细胞增殖。
DOI：
10.1016/s0006-291x(86)80222-4
发表时间：
1986
影响因子：
3.1
作者：
Gordon,EA;Carney,DH
通讯作者：
Carney,DH
影响因子：
3
作者：
MUSTOE, TA;PURDY, J;PIERCE, GF
通讯作者：
PIERCE, GF