Tissue kallikreins: new players in normal and abnormal cell growth?
Tissue kallikreins: new players in normal and abnormal cell growth?
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DOI：
10.1055/s-0037-1613593
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发表时间：
2003-07
影响因子：
6.7
通讯作者：
G. Yousef;E. Diamandis
中科院分区：
文献类型：
--
作者：
G. Yousef;E. Diamandis
摘要丝氨酸蛋白酶是一种催化部位含有活性丝氨酸残基的蛋白水解酶。激肽释放酶是丝氨酸蛋白酶家族的一个亚类，具有多种生理功能。人类组织激肽释放酶基因家族目前已经完全确定，包括15个成员，聚集在染色体19q13.4上300kb的区域。在这篇综述中，我们从DNA、mRNA和蛋白质水平讨论了Kallik-reins的共同结构特征。激肽释放酶以非活性酵素的形式分泌，并被N端肽的裂解激活。一些激肽释放酶可以自我激活，而另一些则可能被其他激肽释放酶或其他蛋白酶激活。大多数激肽释放酶被预测具有胰酶样酶活性，除了三个成员可能具有胰凝乳酶样活性。间接证据表明，至少有一些激肽释放酶可能是酶级联途径的一部分，该途径在侵袭性形式的卵巢癌中被激活，可能还包括其他癌症。越来越多的证据表明激肽释放酶在不同的恶性肿瘤中具有潜在的诊断和/或预后作用。除了PSA，许多其他的Kallik-rein在恶性肿瘤中也有不同的表达。例如，hK6、10和11是诊断卵巢癌的有前景的血清学标志物。KLK10可能是一种肿瘤抑制因子。除了它们的诊断和预后价值，激肽释放酶也可能是很好的治疗靶点。这篇论文的一部分最初是在2002年9月在德国慕尼黑举行的第16届国际纤维蛋白溶解和蛋白分解学会(ISFP)国际大会和第17届国际纤维蛋白原研究会(IFRS)国际纤维蛋白原研讨会的联席会议上提交的。
Summary Serine proteases are proteolytic enzymes with an active serine residue in their catalytic site. Kallikreins are a subgroup of the serine protease family and are known to have diverse physiological functions. The human tissue kallikrein gene family has now been fully characterized and includes 15 members, clustered in a 300 kb region on chromosome 19q13.4. In this review, we discuss the common structural features of kallik-reins at the DNA, mRNA and protein levels. Kallikreins are secreted as inactive zymogens and are activated by cleavage of an N-terminal peptide. Some kallikreins can undergo autoactivation while others may be activated by other kallikreins or other proteases. Most kallikreins are predicted to have trypsin-like enzymatic activity except for three members which may have chymotrypsin-like activity. Circumstantial evidence suggests that at least some kallikreins may be part of an enzymatic cascade pathway which is activated in aggressive forms of ovarian and probably other cancers. Accumulating evidence suggests potential diagnostic and/or prognostic roles of kallikreins in diverse malignancies. In addition to PSA, many other kallik-reins show differential expression in malignancy. For example, hK6, 10 and 11 are promising serological markers for ovarian cancer diagnosis. KLK10 may act as a tumor suppressor. In addition to their diagnostic and prognostic values, kallikreins may also be good therapeutic targets. Part of this paper was originally presented at the joint meetings of the 16th International Congress of the International Society of Fibrinolysis and Proteolysis (ISFP) and the 17th International Fibrinogen Workshop of the International Fibrinogen Research Society (IFRS) held in Munich, Germany, September, 2002.