Lysosomal degradation of receptor-bound urokinase-type plasminogen activator is enhanced by its inhibitors in human trophoblastic choriocarcinoma cells - PubMed (original) (raw)

Lysosomal degradation of receptor-bound urokinase-type plasminogen activator is enhanced by its inhibitors in human trophoblastic choriocarcinoma cells

P H Jensen et al. Cell Regul. 1990 Dec.

Abstract

We have studied the effect of plasminogen activator inhibitors PAI-1 and PAI-2 on the binding of urokinase-type plasminogen activator (u-PA) to its receptor in the human choriocarcinoma cell line JAR. With 125I-labeled ligands in whole-cell binding assays, both uncomplexed u-PA and u-PA-inhibitor complexes bound to the receptor with a Kd of approximately 100 pM at 4 degrees C. Transferring the cells to 37 degrees C led to degradation to amino acids of up to 50% of the cell-bound u-PA-inhibitor complexes, whereas the degradation of uncomplexed u-PA was 15%; the remaining ligand was recovered in an apparently intact form in the medium or was still cell associated. The degradation could be inhibited by inhibitors of vesicle transport and lysosomal hydrolases. By electron microscopic autoradiography, both 125I-u-PA and 125I-u-PA-inhibitor complexes were located over the cell membrane at 4 degrees C, with the highest density of grains over the membrane at cell-cell interphases, but, after incubation at 37 degrees C, 17 and 27% of the grains for u-PA and u-PA-PAI-1 complexes, respectively, appeared over lysosomal-like bodies. These findings suggest that the u-PA receptor possesses a clearance function for the removal of u-PA after its complex formation with a specific inhibitor. The data suggest a novel mechanism by which receptor-mediated endocytosis is initiated by the binding of a secondary ligand.

PubMed Disclaimer

Cited by

Plasmin-dependent elimination of the growth-factor-like domain in urokinase causes its rapid cellular uptake and degradation.
Poliakov A, Tkachuk V, Ovchinnikova T, Potapenko N, Bagryantsev S, Stepanova V. Poliakov A, et al. Biochem J. 2001 May 1;355(Pt 3):639-45. doi: 10.1042/bj3550639. Biochem J. 2001. PMID: 11311125 Free PMC article.
Protein-binding RNA aptamers affect molecular interactions distantly from their binding sites.
Dupont DM, Thuesen CK, Bøtkjær KA, Behrens MA, Dam K, Sørensen HP, Pedersen JS, Ploug M, Jensen JK, Andreasen PA. Dupont DM, et al. PLoS One. 2015 Mar 20;10(3):e0119207. doi: 10.1371/journal.pone.0119207. eCollection 2015. PLoS One. 2015. PMID: 25793507 Free PMC article.
alpha 2-Antiplasmin and plasminogen activator inhibitors in healing human skin wounds.
Schaefer BM, Maier K, Eickhoff U, Bechtel M, Kramer MD. Schaefer BM, et al. Arch Dermatol Res. 1996 Mar;288(3):122-8. doi: 10.1007/BF02505820. Arch Dermatol Res. 1996. PMID: 8967779
Analysis of a two-domain binding site for the urokinase-type plasminogen activator-plasminogen activator inhibitor-1 complex in low-density-lipoprotein-receptor-related protein.
Andersen OM, Petersen HH, Jacobsen C, Moestrup SK, Etzerodt M, Andreasen PA, Thøgersen HC. Andersen OM, et al. Biochem J. 2001 Jul 1;357(Pt 1):289-96. doi: 10.1042/0264-6021:3570289. Biochem J. 2001. PMID: 11415462 Free PMC article.
Localization of urokinase-type plasminogen activator, plasminogen activator inhibitor-1, 2 and plasminogen in colon cancer.
Naitoh H, Eguchi Y, Ueyama H, Kodama M, Hattori T. Naitoh H, et al. Jpn J Cancer Res. 1995 Jan;86(1):48-56. doi: 10.1111/j.1349-7006.1995.tb02987.x. Jpn J Cancer Res. 1995. PMID: 7737909 Free PMC article.

References

1. Cell. 1976 Oct;9(2):231-40 - PubMed
1. J Cell Biol. 1977 Jan;72(1):161-73 - PubMed
1. N Engl J Med. 1977 May 5;296(18):1017-23 - PubMed
1. Cell Tissue Res. 1978 Nov 20;194(2):207-18 - PubMed
1. FEBS Lett. 1980 Dec 1;121(2):275-9 - PubMed

Lysosomal degradation of receptor-bound urokinase-type plasminogen activator is enhanced by its inhibitors in human trophoblastic choriocarcinoma cells - PubMed (original) (raw)