Historical Background
The receptor (uPAR) for the urokinase-type plasminogen activator (uPA) was firstly identified in 1985 on the surface of monocyte-like cells but only in 1990 uPAR protein was purified and cDNA cloned and sequenced. The first role proposed for uPAR was the focusing of the uPA proteolytic activity on the cell membrane, thus allowing cell migration through the extracellular matrix (ECM), without affecting the general architecture of the tissue. Since then, a large body of evidence clearly showed various roles for uPAR, independent of uPA enzymatic activity. In fact, uPAR is able to transduce proliferation, differentiation, adhesion, and migration signals into the cells, despite the absence of a transmembrane region and a cytosolic tail. However, the ability of uPAR to focus uPA activity on the cell membrane attributed to this specific receptor a key role in the plasminogen...
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References
Aguirre-Ghiso JA, Estrada Y, Liu D, Ossowski LERK. (MAPK) activity as a determinant of tumor growth and dormancy; regulation by p38(SAPK). Cancer Res. 2003;63:1684–95.
Balsara RD, Ploplis VA. Plasminogen activator inhibitor-1: the double-edged sword in apoptosis. Thromb Haemost. 2008;100:1029–36.
Blasi F, Sidenius N. The urokinase receptor: focused cell surface proteolysis, cell adhesion and signaling. FEBS Lett. 2010;584:1923–30.
Carriero MV, Franco P, Vocca I, Alfano D, Longanesi-Cattani I, Bifulco K, Mancini A, Caputi M, Stoppelli MP. Structure, function and antagonists of urokinase-type plasminogen activator. Front Biosci. 2009;(14):3782–94.
Castellino FJ, Ploplis VA. Structure and function of the plasminogen/plasmin system. Thromb Haemost. 2005;93:647–54.
Gargiulo L, Longanesi-Cattani I, Bifulco K, Franco P, Raiola R, Campiglia P, Grieco P, Peluso G, Stoppelli MP, Carriero MV. Cross-talk between fMLP and vitronectin receptors triggered by urokinase receptor-derived SRSRY peptide. J Biol Chem. 2005;280:25225–32.
Irigoyen JP, Muñoz-Cánoves P, Montero L, Koziczak M, Nagamine Y. The plasminogen activator system: biology and regulation. Cell Mol Life Sci. 1999;56:104–32.
Kjaergaard M, Hansen LV, Jacobsen B, Gardsvoll H, Ploug M. Structure and ligand interactions of the urokinase receptor (uPAR). Front Biosci. 2008;(13):5441–61.
Le Y, Murphy PM, Wang JM. Formyl-peptide receptors revisited. Trends Immunol. 2002;23:541–8.
Madsen CD, Sidenius N. The interaction between urokinase receptor and vitronectin in cell adhesion and signalling. Eur J Cell Biol. 2008;87:617–29.
Margheri F, Manetti M, Serratì S, Nosi D, Pucci M, Matucci-Cerinic M, Kahaleh B, Bazzichi L, Fibbi G, Ibba-Manneschi L, Del Rosso M. Domain 1 of the urokinase-type plasminogen activator receptor is required for its morphologic and functional, beta2 integrin-mediated connection with actin cytoskeleton in human microvascular endothelial cells: failure of association in systemic sclerosis endothelial cells. Arthritis Rheum. 2006;54:3926–38.
Medcalf RL, Stasinopoulos SJ. The undecided serpin. The ins and outs of plasminogen activator inhibitor type 2. FEBS J. 2005;272:4858–67.
Montuori N, Visconte V, Rossi G, Ragno P. Soluble and cleaved forms of the urokinase-receptor: degradation products or active molecules? Thromb Haemost. 2005;93:192–8.
Montuori N, Bifulco K, Carriero MV, La Penna C, Visconte V, Alfano D, Pesapane A, Rossi FW, Salzano S, Rossi G, Ragno P. The cross-talk between the urokinase receptor and fMLP receptors regulates the activity of the CXCR4 chemokine receptor. Cell Mol Life Sci. 2010. doi:10.1007/s00018-010-0564-7.
Nagamine Y, Medcalf RL, Muñoz-Cánoves P. Transcriptional and potsttranscriptional regulation of the plasminogen activator system. Thromb Haemost. 2005;93:661–75.
Ragno P. The urokinase receptor: a ligand or a receptor? Story of a sociable molecule. Cell Mol Life Sci. 2006;63:1028–37.
Ragno P, Blasi F. uPAR and proteases in mobilization of hematopoietic stem cells. In: Edwards D, Hoyer-Hansen G, Blasi F, Sloane BF, editors. The Cancerdegradome. New York: Springer; 2008. p. 433–50.
Rijken DC, Lijnen HR. New insights into the molecular mechanisms of the fibrinolytic system. J Thromb Haemost. 2009;7:4–13.
Smith HW, Marshall CJ. Regulation of cell signalling by uPAR. Nat Rev Mol Cell Biol. 2010;11:23–36.
Tang CH, Wei Y. The urokinase receptor and integrins in cancer progression. Cell Mol Life Sci. 2008;65:1916–32.
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Ragno, P. (2018). Structure and Functions of the Urokinase Receptor. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_536
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DOI: https://doi.org/10.1007/978-3-319-67199-4_536
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