The urokinase receptor as an entertainer of signal transduction

Silvia D'Alessio, Francesco Blasi

Research output: Contribution to journalArticle

Abstract

The serine-protease urokinase (uPA) and its specific membrane receptor uPAR controls matrix degradation through the conversion of plasminogen into plasmin and play a crucial role in a number of biological processes including local fibrinolysis, inflammation, angiogenesis, matrix remodelling during wound healing, tumor invasion and metastasis. Most of the cellular responses modulated by the uPA/uPAR system, including migration, cellular adhesion, differentiation, proliferation and apoptosis require transmembrane signaling, which is mediated by direct contacts of uPAR with a variety of extracellular proteins and membrane receptors, such as integrins, EGF receptor, high molecular weight kininogen, caveolin and the G-protein-coupled receptor FPRL1. As a result of these interactions, uPAR activates intracellular signalling molecules such as tyrosine-and serine-protein kinases, Src, focal adhesion kinase (FAK), Rac, extracellular-signal-regulated kinase (ERK)/mitogenactivated protein kinase (MAPK) and JAK/STAT, being part of a large "signalosome" interacting with several molecules on both the outside and inside of the cell. This review is focused on the biochemistry of the pathways affected by uPAR and its partners.

Original languageEnglish
Pages (from-to)4575-4587
Number of pages13
JournalFrontiers in Bioscience
Volume14
Issue number12
DOIs
Publication statusPublished - Jan 1 2009

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High Molecular Weight Kininogens
Caveolins
Biological Phenomena
Focal Adhesion Protein-Tyrosine Kinases
Signal transduction
Plasminogen
Protein-Serine-Threonine Kinases
Fibrinolysin
Extracellular Signal-Regulated MAP Kinases
Urokinase-Type Plasminogen Activator
Serine Proteases
Fibrinolysis
G-Protein-Coupled Receptors
Epidermal Growth Factor Receptor
Integrins
Biochemistry
Protein-Tyrosine Kinases
Wound Healing
Protein Kinases
Signal Transduction

Keywords

  • Cell adhesion
  • Cell migration
  • Cell signalling
  • Egfr
  • Integrins
  • MAPkinases
  • Review
  • Signal transduction
  • Tumor invasion
  • uPA
  • uPAR

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Medicine(all)

Cite this

The urokinase receptor as an entertainer of signal transduction. / D'Alessio, Silvia; Blasi, Francesco.

In: Frontiers in Bioscience, Vol. 14, No. 12, 01.01.2009, p. 4575-4587.

Research output: Contribution to journalArticle

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