Ragno P, Montuori N, Rossi G
Centro di Endocrinologia ed Oncologia Sperimentale (CEOS), Consiglio Nazionale delle Ricerche, Naples, Italy.
Eur J Biochem. 1995 Oct 15;233(2):514-9. doi: 10.1111/j.1432-1033.1995.514_2.x.
The urokinase-type plasminogen activator (uPA) and its inhibitor PAI-2 form a covalent complex that, upon binding to the uPA receptor (uPA-R), is cleaved into two fragments of molecular masses 70 kDa and 22 kDa. The 70-kDa fragment results from the interaction of the B chain of uPA and PAI-2 whereas the 22-kDa fragment is the A chain of the enzyme [13]. We prove that, at 37 degrees C, the 70-kDa fragment is released into the medium, whereas the 22-kDa fragment remains bound to the cell surface. uPA complexed with its other specific inhibitor, PAI-1, is cleaved into fragments of identical sizes, but the 70-kDa component is internalized via the alpha 2-macroglobulin receptor. At 4 degrees C, both uPA/PAI-2 complex degradation products remain bound to the uPA-R. We propose that the 70-kDa molecule, which lacks the uPA binding region for uPA-R, is bound to uPA-R via a new binding site, unmasked only when uPA-R is occupied by uPA/PAI-2 complexes.
尿激酶型纤溶酶原激活剂（uPA）及其抑制剂PAI-2形成一种共价复合物，该复合物与uPA受体（uPA-R）结合后，会被切割成分子量分别为70 kDa和22 kDa的两个片段。70 kDa片段是由uPA的B链与PAI-2相互作用产生的，而22 kDa片段则是该酶的A链[13]。我们证明，在37℃时，70 kDa片段会释放到培养基中，而22 kDa片段仍与细胞表面结合。与另一种特异性抑制剂PAI-1复合的uPA会被切割成相同大小的片段，但70 kDa成分会通过α2-巨球蛋白受体内化。在4℃时，两种uPA/PAI-2复合物降解产物均与uPA-R结合。我们提出，缺乏uPA与uPA-R结合区域的70 kDa分子通过一个新的结合位点与uPA-R结合，该位点只有在uPA-R被uPA/PAI-2复合物占据时才会暴露。
