Kjøller L, Simonsen A C, Ellgaard L, Andreasen P A
Department of Molecular Biology, University of Aarhus, Denmark.
Mol Cell Endocrinol. 1995 Apr 1;109(2):209-17. doi: 10.1016/0303-7207(95)03504-z.
Complex between urokinase and its type-1 inhibitor (uPA-PAI-1) may, when bound to the urokinase receptor (uPAR), be endocytosed by an ensuing binding of the complex to the multiligand receptors alpha (2)-macroglobulin receptor/low density lipoprotein receptor-related protein (alpha 2MR/LRP) and glycoprotein 330 (gp330). We have found that phorbol esters regulate endocytosis of uPA-PAI-1 differently in different cell lines. In COS-1 cells, expressing uPAR and high levels of alpha 2MR/LRP under basal conditions, phorbol esters cause a time-dependent decrease in endocytosis concomitantly with a parallel down-regulation of alpha 2MR/LRP expression. An up-regulation of uPAR expression was also observed. General endocytosis via the clathrin-coated pit pathway was not affected by PMA treatment, as judged from measurements of transferrin endocytosis. In LLC-PK1 cells, expressing alpha 2MR/LRP but not uPAR under basal conditions, phorbol esters transiently increase endocytosis in parallel with a transient induction of uPAR expression, while there was virtually no change in alpha 2MR/LRP expression. Differential regulation of endocytosis therefore seems to be caused by differential regulation of the receptors, with either the alpha 2MR/LRP-level (in COS)-1 cells) or the uPAR-level (in LLC-PK1 cells) being rate-limiting.
尿激酶与其1型抑制剂（uPA-PAI-1）形成的复合物，当与尿激酶受体（uPAR）结合时，可能会通过该复合物随后与多配体受体α(2)-巨球蛋白受体/低密度脂蛋白受体相关蛋白（α2MR/LRP）和糖蛋白330（gp330）的结合而被内吞。我们发现佛波酯在不同细胞系中对uPA-PAI-1的内吞作用有不同的调节。在COS-1细胞中，在基础条件下表达uPAR和高水平的α2MR/LRP，佛波酯会导致内吞作用随时间下降，同时α2MR/LRP表达平行下调。还观察到uPAR表达上调。从转铁蛋白内吞作用的测量判断，通过网格蛋白包被小窝途径的一般内吞作用不受PMA处理的影响。在LLC-PK1细胞中，在基础条件下表达α2MR/LRP但不表达uPAR，佛波酯会使内吞作用短暂增加，同时uPAR表达短暂诱导，而α2MR/LRP表达几乎没有变化。因此，内吞作用的差异调节似乎是由受体的差异调节引起的，在COS-1细胞中是α2MR/LRP水平，在LLC-PK1细胞中是uPAR水平起限速作用。
