Cavallaro U, Soria M R
Department of Biological and Technological Research, San Raffaele Scientific Institute, Milano, Italy.
Semin Cancer Biol. 1995 Oct;6(5):269-78. doi: 10.1006/scbi.1995.0035.
We have conjugated the ribosome-inactivating protein (RIP) saporin to human urokinase-type plasminogen activator (uPA), and tested the uPA-saporin conjugate for cytotoxicity to uPA receptor-expressing cells. Unlike unconjugated uPA, saporin-conjugated uPA did not require any interaction with plasminogen activator inhibitors to be internalized. We have shown that saporin, as well as other RIPs, binds to the alpha 2-macroglobulin receptor (alpha 2 MR), a cell surface glycoprotein that endocytoses uPA-inhibitor complexes. Thus, the uPA receptor might present uPA saporm to alpha 2MR for internalization of the conjugate, a mechanism similar to that of uPA complexed to specific PA inhibitors. The binding of RIPs to alpha 2MR contrasts with previously proposed non-specific mechanisms for RIP entry into cells. The implications of the interactions between RIPs and alpha 2MR are discussed, with an emphasis on the role of alpha 2MR in mediating RIP immunogenicity and immune suppression.
我们已将核糖体失活蛋白（RIP）皂草素与人类尿激酶型纤溶酶原激活剂（uPA）偶联，并测试了uPA-皂草素偶联物对表达uPA受体的细胞的细胞毒性。与未偶联的uPA不同，皂草素偶联的uPA不需要与纤溶酶原激活剂抑制剂发生任何相互作用就能被内化。我们已经表明，皂草素以及其他RIPs与α2-巨球蛋白受体（α2MR）结合，α2MR是一种能内吞uPA-抑制剂复合物的细胞表面糖蛋白。因此，uPA受体可能会将uPA-皂草素呈递给α2MR，以使偶联物内化，这一机制类似于与特定PA抑制剂复合的uPA的机制。RIPs与α2MR的结合与之前提出的RIP进入细胞的非特异性机制形成对比。本文讨论了RIPs与α2MR之间相互作用的意义，重点强调了α2MR在介导RIP免疫原性和免疫抑制中的作用。
