Atkinson S J, Patterson M L, Butler M J, Murphy G
School of Biological Sciences, University of East Anglia, NR4 7TJ, Norwich, UK.
FEBS Lett. 2001 Mar 2;491(3):222-6. doi: 10.1016/s0014-5793(01)02204-9.
A fibrosarcoma cell line transfected with the matrix metalloproteinase MT1 MMP showed an enhanced ability to degrade 14C-labelled collagen films. As previously shown for proMMP 2 activation, TIMP 1 was an ineffective inhibitor of the process of collagenolysis whereas TIMP 2 was efficient and completely prevented collagen degradation. In the presence of the calcium ionophore, ionomycin, proteolytic processing of MT1 MMP was restricted and collagenolysis did not occur indicating that the 63 kDa form of the enzyme is not a functional collagenase. The collagenolytic activity of MT1 MMP was shown to be enhanced by the addition of proMMP 2, but TIMP 1 inhibition remained poor relative to that of TIMP 2. The study demonstrated that synergy between two non-conventional collagenases effectively degrades insoluble pericellular collagen. Due to the membrane localisation of MT1 MMP, this could potentially occur in a highly localised manner.
用基质金属蛋白酶MT1-MMP转染的纤维肉瘤细胞系显示出更强的降解14C标记胶原膜的能力。如先前对proMMP-2激活所显示的那样，TIMP-1是胶原溶解过程的无效抑制剂，而TIMP-2是有效的，并且完全阻止了胶原降解。在钙离子载体离子霉素存在的情况下，MT1-MMP的蛋白水解加工受到限制，胶原溶解未发生，这表明该酶的63 kDa形式不是功能性胶原酶。通过添加proMMP-2可增强MT1-MMP的胶原溶解活性，但相对于TIMP-2，TIMP-1的抑制作用仍然较弱。该研究表明，两种非常规胶原酶之间的协同作用有效地降解了不溶性细胞周胶原。由于MT1-MMP的膜定位，这可能以高度局部化的方式发生。
