The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
Is plasminogen activator inhibitor-1 the molecular switch that governs urokinase receptor-mediated cell adhesion and release?
Open accessAbstract
Induction of the urokinase type plasminogen activator receptor (uPAR) promotes cell adhesion through its interaction with vitronectin (VN) in the extracellular matrix, and facilitates cell migration and invasion by localizing uPA to the cell surface. We provide evidence that this balance between cell adhesion and cell detachment is governed by PA inhibitor-1 (PAI-1). First, we demonstrate that uPAR and PAI-1 bind to the same site in VN (i.e., the amino-terminal somatomedin B domain; SMB), and that PAI-1 competes with uPAR for binding to SMB. Domain swapping and mutagenesis studies indicate that the uPAR-binding sequence is located within the central region of the SMB domain, a region previously shown to contain the PAI-1-binding motif. Second, we show that PAI-1 dissociates bound VN from uPAR and detaches U937 cells from their VN substratum. This PAI-1 mediated release of cells from VN appears to occur independently of its ability to function as a protease inhibitor, and may help to explain why high PAI-1 levels indicate a poor prognosis for many cancers. Finally, we show that uPA can rapidly reverse this effect of PAI-1. Taken together, these results suggest a dynamic regulatory role for PAI-1 and uPA in uPAR-mediated cell adhesion and release.
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Cites
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CHAPLAIN, M. A. J., & LOLAS, G. (2005) · Mathematical Models and Methods in Applied Sciences · doi:10.1142/s0218202505000947 · Cited by 323
The urokinase plasminogen activator system: a target for anti-cancer therapy
Ulisse, S., Baldini, E., Sorrenti, S., & D'Armiento, M. (2009) · Current Cancer Drug Targets · doi:10.2174/156800909787314002 · Cited by 312
Czekay, R.-P., Aertgeerts, K., Curriden, S. A., & Loskutoff, D. J. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200208117 · Cited by 304
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Valle Oseguera, C. A., & Spencer, J. V. (2017) · Cancer Cell International · doi:10.1186/s12935-017-0399-5 · Cited by 24
Metadata
- Authors
- Deng, G., Curriden, S. A., Wang, S., Rosenberg, S., & Loskutoff, D. J.
- Venue
- The Journal of cell biology
- Publisher
- Rockefeller University Press
- Published
- 1996-09-15
- Volume
- 134
- Issue
- 6
- Pages
- 1563-1571
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- OpenAlex
- W2102577298
- Cited by
- 448
- References
- 45
- FWCI
- 16.01
- Type
- journal article
- Language
- en
- Open access
- green
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- The paper
- Deng, G., Curriden, S. A., Wang, S., Rosenberg, S., & Loskutoff, D. J. (1996). Is plasminogen activator inhibitor-1 the molecular switch that governs urokinase receptor-mediated cell adhesion and release? The Journal of cell biology. https://doi.org/10.1083/jcb.134.6.1563
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
