Ossowski, L. & Aguirre-Ghiso, J.A. Urokinase-receptor and integrin partnership: Coordination of signaling for cell adhesion, migration and growth. Curr. Opin. Cell. Biol. 12, 613-620

Rochelle Belfer Chemotherapy Foundation, Division of Medical Oncology, Department of Medicine, Box 1178, Mount Sinai School of Medicine, New York, New York 11029, USA.
Current Opinion in Cell Biology (Impact Factor: 8.47). 11/2000; 12(5):613-20. DOI: 10.1016/S0955-0674(00)00140-X
Source: PubMed


Urokinase-type plasminogen activator receptor (uPAR) binds the urokinase-type plasminogen activator (uPA) and facilitates a proteolytic cascade focused at the cell surface. More recently, uPAR was recognized as a multifunctional protein that, through its interactions with integrins, initiates signaling events that alter cell adhesion, migration and proliferation. Results obtained recently have led to new insights into the structural aspects of uPAR interaction with integrins, provided a more detailed description of the signaling pathway they induce, and determined that uPAR signaling plays a role in cell migration and tumorigenicity.

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Available from: Julio Aguirre-Ghiso,
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    • "[58] [59] [60] [61] uPAR is capable of catalyzing the conversion of plasminogen to plasmin, an important molecule in fibrinolytic processes and in the activation of several matrix metalloproteinases, in the recycling and degradation of the extracellular matrix, in cell activation, migration, contraction, vasculogenesis and in vitronectin interaction and degradation. [51] [62] [63] [64] [65] [66] This phenomenon may occur in plasma, on the podocyte surface or in renal distal tubular cells. [16] [23] Patients with NS present elevated serum levels of plasminogen and plasmin. "
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    • "However, the role of the uPAR-α5β1 integrin signaling pathway in apoptosis is poorly understood. Crosstalk between uPAR and p53 [6], and caveolin-induced uPAR-dependent ERK activation [7] have also been reported. "
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    ABSTRACT: Urokinase receptor interacts with α5β1-integrin and enhances cancer cell proliferation and metastasis. Activation of α5β1-integrin requires caveolin-1 and is regulated by uPAR, which upregulates persistently the activated ERK necessary for tumor growth. In this study, we show that the ganglioside GT1b induces proapoptotic signaling through two uPAR-ERK signaling pathways in A549 lung cancer cells. GT1b downregulated the expression of α5β1 integrin, caveolin-1, fibronectin, FAK, and ERK, whereas GT1b upregulated the expression of p53 and uPAR, suggesting GT1b mediated depletion of caveolin-1 in uPAR-expressing A549 cells also disrupts uPAR/integrin complexes, resulting in downregulation of fibronectin-α5β1-integrin-ERK signaling. Following p53 siRNA treatment, FAK and ERK expression was recovered, meaning the presence of reentry uPAR-FAK-ERK signaling pathway. These findings reveal that GT1b is involved in both caveolin-1-dependent uPAR-α5β1-integrin-ERK signaling and caveolin-1-independent uPAR-FAK-ERK signaling. These results suggest a novel function of GT1b as a dual regulator of ERK by modulating caveolin-1 and p53.
    American Journal of Cancer Research 12/2014; 4(6):801-10. · 4.17 Impact Factor
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    • "uPAR is a cell membrane-anchored binding protein. uPA accumulates plasminogen activation activity at cell surfaces (Ossowski and Aguirre-Ghiso 2000). uPA is the primary cellular activator which converts the pro-enzyme plasminogen into its active form plasmin (Irigoyen et al. 1999). "
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    ABSTRACT: Tripeptides of the general X-SO2-d-Ser-AA-Arg-CO-Y formula, where X = α-tolyl, p-tolyl, 2,4,6-triisopropylphenyl; AA = alanine, glycine, norvaline and Y = OH, NH-(CH2)5NH2 were obtained and tested for their effect on the amidolytic activities of urokinase, thrombin, trypsin, plasmin, t-PA and kallikrein. The most active compound towards urokinase was PhCH2SO2-d-Ser-Gly-Arg-OH with Ki value 5.4 μM and the most active compound toward thrombin was PhCH2SO2-d-Ser-NVa-Arg-OH with Ki value 0.82 μM. The peptides were nontoxic against porcine erythrocytes in vitro. PhCH2SO2-d-Ser-Gly-Arg-OH showed cytotoxic effect against DLD cell lines with IC50 values of 5 μM. For the highly selective determination of the interaction of some of the synthesised acids of tripeptides with urokinase and plasmin the Surface Plasmon Resonance Imaging sensor has been applied. These compounds bind to urokinase and plasmin in 0.05 mM concentration.
    International Journal of Peptide Research and Therapeutics 09/2013; 19(3):191-198. DOI:10.1007/s10989-012-9338-4 · 0.91 Impact Factor
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