Obiezu Chistina V, Michael Iacovos P, Levesque Michael A, Diamandis Eleftherios P
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Avenue, and Department of Laboratory Medicine and Pathobiology, University of Toronto, 100 College Street, Toronto M5G 1L5, ON, Canada.
Biol Chem. 2006 Jun;387(6):749-59. doi: 10.1515/BC.2006.094.
Human kallikrein 4 (hK4) is a member of the expanded family of human kallikreins, a group of 15 secreted proteases. While this protein has been associated with ovarian and prostate cancer prognosis, only limited functional information exists. Therefore, we have undertaken an investigation of its enzymatic properties regarding substrate preference, degradation of extracellular matrix proteins, and its inhibition by various inhibitors. We successfully expressed and purified active recombinant hK4 from supernatants of the Pichia pastoris expression system. This enzyme seems to cleave more efficiently after Arg compared to Lys at the P1 position and exhibits modest specificity for amino acids at positions P2 and P3. hK4 forms complexes with alpha1-antitrypsin, alpha2-antiplasmin and alpha2-macroglobulin. The protease mediates limited degradation of extracellular matrix proteins such as collagen I and IV, and more efficient degradation of the alpha-chain of fibrinogen. The cleavage of extracellular matrix proteins by hK4 suggests that this enzyme may play a role in tissue remodeling and cancer metastasis.
人激肽释放酶4（hK4）是扩展的人激肽释放酶家族成员，该家族由15种分泌型蛋白酶组成。虽然这种蛋白质与卵巢癌和前列腺癌的预后有关，但目前仅有有限的功能信息。因此，我们对其酶学特性进行了研究，包括底物偏好、细胞外基质蛋白的降解以及各种抑制剂对其的抑制作用。我们成功地从毕赤酵母表达系统的上清液中表达并纯化了活性重组hK4。与P1位置的赖氨酸相比，该酶似乎在精氨酸后切割效率更高，并且对P2和P3位置的氨基酸表现出适度的特异性。hK4与α1-抗胰蛋白酶、α2-抗纤溶酶和α2-巨球蛋白形成复合物。该蛋白酶介导细胞外基质蛋白如I型和IV型胶原的有限降解，以及纤维蛋白原α链的更有效降解。hK4对细胞外基质蛋白的切割表明该酶可能在组织重塑和癌症转移中发挥作用。
