Murphy G, Stanton H, Cowell S, Butler G, Knäuper V, Atkinson S, Gavrilovic J
School of Biological Sciences, University of East Anglia, Norwich, UK.
APMIS. 1999 Jan;107(1):38-44. doi: 10.1111/j.1699-0463.1999.tb01524.x.
The activation of pro matrix metalloproteinases (MMPs) by sequential proteolysis of the propeptide blocking the active site cleft is regarded as one of the key levels of regulation of these proteinases. Potential physiological mechanisms including cell-associated plasmin generation by urokinase-like plasminogen activator, or the action of cell surface MT1-MMPs appear to be involved in the initiation of cascades of pro MMP activation. Gelatinase A, collagenase 3 and gelatinase B may be activated by MT-MMP based mechanisms, as evidenced by both biochemical and cell based studies. Hence the regulation of MT-MMPs themselves becomes critical to the determination of MMP activity. This includes activation, assembly at the cell surfaces as TIMP-2 complexes and subsequent inactivation by proteolysis or TIMP inhibition.
通过对封闭活性位点裂隙的前肽进行顺序蛋白水解来激活前基质金属蛋白酶（MMPs），被视为这些蛋白酶调控的关键水平之一。潜在的生理机制，包括尿激酶型纤溶酶原激活剂产生细胞相关的纤溶酶，或细胞表面MT1-MMP的作用，似乎参与了前MMP激活级联反应的起始。明胶酶A、胶原酶3和明胶酶B可能通过基于MT-MMP的机制被激活，生化研究和细胞研究均证明了这一点。因此，MT-MMP自身的调控对于确定MMP活性至关重要。这包括激活、作为TIMP-2复合物在细胞表面组装，以及随后通过蛋白水解或TIMP抑制而失活。
