Ramsay Andrew J, Reid Janet C, Adams Mark N, Samaratunga Hemamali, Dong Ying, Clements Judith A, Hooper John D
Institute of Health and Biomedical Innovation, Queensland University of Technology, 6 Musk Avenue, Kelvin Grove, Queensland 4059, Australia.
Biol Chem. 2008 Jun;389(6):653-68. doi: 10.1515/BC.2008.078.
The prostate is a site of high expression of serine proteinases including members of the kallikrein-related peptidase (KLK) family, as well as other secreted and membrane-anchored serine proteinases. It has been known for some time that members of this enzyme family elicit cellular responses by acting directly on cells. More recently, it has been recognised that for serine proteinases with specificity for cleavage after arginine and lysine residues (trypsin-like or tryptic enzymes) these cellular responses are often mediated by cleavage of members of the proteinase-activated receptor (PAR) family--a four member sub-family of G protein-coupled receptors. Here, we review the expression of PARs in prostate, the ability of prostatic trypsin-like KLKs and other prostate-expressed tryptic enzymes to cleave PARs, as well as the prostate cancer-associated consequences of PAR activation. In addition, we explore the dysregulation of trypsin-like serine proteinase activity through the loss of normal inhibitory mechanisms and potential interactions between these dysregulated enzymes leading to aberrant PAR activation, intracellular signalling and cancer-promoting cellular changes.
前列腺是丝氨酸蛋白酶高表达的部位，包括激肽释放酶相关肽酶（KLK）家族成员以及其他分泌型和膜锚定丝氨酸蛋白酶。一段时间以来，人们已经知道该酶家族成员通过直接作用于细胞引发细胞反应。最近，人们认识到，对于在精氨酸和赖氨酸残基后具有切割特异性的丝氨酸蛋白酶（胰蛋白酶样或胰蛋白酶类酶），这些细胞反应通常是由蛋白酶激活受体（PAR）家族成员的切割介导的，PAR家族是G蛋白偶联受体的一个四成员亚家族。在这里，我们综述PARs在前列腺中的表达、前列腺胰蛋白酶样KLKs和其他前列腺表达的胰蛋白酶类酶切割PARs的能力，以及PAR激活与前列腺癌相关的后果。此外，我们探讨了由于正常抑制机制丧失导致的胰蛋白酶样丝氨酸蛋白酶活性失调，以及这些失调酶之间潜在的相互作用，这些相互作用导致异常的PAR激活、细胞内信号传导和促进癌症的细胞变化。
