Urokinase receptor

Function

Urokinase receptor or Urokinase plasminogen activator surface receptor or CD87 (uPAR) plays an important role in migration of T cells^[1]. uPAR is a GPI-anchored membrane protein. It triggers cell signalling and regulates gene expression within the cell. The invasive potential of uPAR expressing tumor cells is modulated by interaction with

urokinase plasminogen activator (uPA)^[2].

Disease

uPAR can control the shift between tumor dormancy and proliferation to form metastasis^[3]

Relevance

Elevated levels of soluble uPAR are associated with kidney disease^[4]. uPAR which is expressed at high levels in malignant tumors is an attractive target for treatment of cancer^[5]. uPAR activity in cancer cells may counteract the activity of anticancer drugs^[6].

Structural highlights

The binding of uPAR and urokinase-type plasminogen activator (uPA) is mediated by hydrophobic numerous interactions. ^[7].

3D structures of urokinase receptor

Urokinase plasminogen activator surface receptor 3D structures

References

↑ Nykjaer A, Møller B, Todd RF 3rd, Christensen T, Andreasen PA, Gliemann J, Petersen CM. Urokinase receptor. An activation antigen in human T lymphocytes. J Immunol. 1994 Jan 15;152(2):505-16 PMID:8283034
↑ Ossowski L, Clunie G, Masucci MT, Blasi F. In vivo paracrine interaction between urokinase and its receptor: effect on tumor cell invasion. J Cell Biol. 1991 Nov;115(4):1107-12. PMID:1659573 doi:10.1083/jcb.115.4.1107
↑ Mauro CD, Pesapane A, Formisano L, Rosa R, D'Amato V, Ciciola P, Servetto A, Marciano R, Orsini RC, Monteleone F, Zambrano N, Fontanini G, Servadio A, Pignataro G, Grumetto L, Lavecchia A, Bruzzese D, Iaccarino A, Troncone G, Veneziani BM, Montuori N, Placido S, Bianco R. Urokinase-type plasminogen activator receptor (uPAR) expression enhances invasion and metastasis in RAS mutated tumors. Sci Rep. 2017 Aug 24;7(1):9388. PMID:28839232 doi:10.1038/s41598-017-10062-1
↑ Hayek SS, Sever S, Ko YA, Trachtman H, Awad M, Wadhwani S, Altintas MM, Wei C, Hotton AL, French AL, Sperling LS, Lerakis S, Quyyumi AA, Reiser J. Soluble Urokinase Receptor and Chronic Kidney Disease. N Engl J Med. 2015 Nov 12;373(20):1916-25. PMID:26539835 doi:10.1056/NEJMoa1506362
↑ Zhai BT, Tian H, Sun J, Zou JB, Zhang XF, Cheng JX, Shi YJ, Fan Y, Guo DY. Urokinase-type plasminogen activator receptor (uPAR) as a therapeutic target in cancer. J Transl Med. 2022 Mar 18;20(1):135. PMID:35303878 doi:10.1186/s12967-022-03329-3
↑ Gonias SL, Hu J. Urokinase receptor and resistance to targeted anticancer agents. Front Pharmacol. 2015 Jul 27;6:154. PMID:26283964 doi:10.3389/fphar.2015.00154
↑ Barinka C, Parry G, Callahan J, Shaw DE, Kuo A, Bdeir K, Cines DB, Mazar A, Lubkowski J. Structural basis of interaction between urokinase-type plasminogen activator and its receptor. J Mol Biol. 2006 Oct 20;363(2):482-95. Epub 2006 Aug 26. PMID:16979660 doi:10.1016/j.jmb.2006.08.063

Human uPAR (grey) complex with glycosylated uPA (magenta) and sulfate (PDB code 2i9b)

Drag the structure with the mouse to rotate

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Michal Harel, Alexander Berchansky

[1] Nykjaer A, Møller B, Todd RF 3rd, Christensen T, Andreasen PA, Gliemann J, Petersen CM. Urokinase receptor. An activation antigen in human T lymphocytes. J Immunol. 1994 Jan 15;152(2):505-16 PMID:8283034

[2] Ossowski L, Clunie G, Masucci MT, Blasi F. In vivo paracrine interaction between urokinase and its receptor: effect on tumor cell invasion. J Cell Biol. 1991 Nov;115(4):1107-12. PMID:1659573 doi:10.1083/jcb.115.4.1107

[3] Mauro CD, Pesapane A, Formisano L, Rosa R, D'Amato V, Ciciola P, Servetto A, Marciano R, Orsini RC, Monteleone F, Zambrano N, Fontanini G, Servadio A, Pignataro G, Grumetto L, Lavecchia A, Bruzzese D, Iaccarino A, Troncone G, Veneziani BM, Montuori N, Placido S, Bianco R. Urokinase-type plasminogen activator receptor (uPAR) expression enhances invasion and metastasis in RAS mutated tumors. Sci Rep. 2017 Aug 24;7(1):9388. PMID:28839232 doi:10.1038/s41598-017-10062-1

[4] Hayek SS, Sever S, Ko YA, Trachtman H, Awad M, Wadhwani S, Altintas MM, Wei C, Hotton AL, French AL, Sperling LS, Lerakis S, Quyyumi AA, Reiser J. Soluble Urokinase Receptor and Chronic Kidney Disease. N Engl J Med. 2015 Nov 12;373(20):1916-25. PMID:26539835 doi:10.1056/NEJMoa1506362

[5] Zhai BT, Tian H, Sun J, Zou JB, Zhang XF, Cheng JX, Shi YJ, Fan Y, Guo DY. Urokinase-type plasminogen activator receptor (uPAR) as a therapeutic target in cancer. J Transl Med. 2022 Mar 18;20(1):135. PMID:35303878 doi:10.1186/s12967-022-03329-3

[6] Gonias SL, Hu J. Urokinase receptor and resistance to targeted anticancer agents. Front Pharmacol. 2015 Jul 27;6:154. PMID:26283964 doi:10.3389/fphar.2015.00154

[7] Barinka C, Parry G, Callahan J, Shaw DE, Kuo A, Bdeir K, Cines DB, Mazar A, Lubkowski J. Structural basis of interaction between urokinase-type plasminogen activator and its receptor. J Mol Biol. 2006 Oct 20;363(2):482-95. Epub 2006 Aug 26. PMID:16979660 doi:10.1016/j.jmb.2006.08.063

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