Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital

The structure and function of the urokinase receptor, a membrane protein governing plasminogen activation on the cell surface

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Tumor cell MT1-MMP is dispensable for osteosarcoma tumor growth, bone degradation and lung metastasis

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. The collagen receptor uPARAP/Endo180 regulates collectins through unique structural elements in its FNII domain

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Cellular uptake of collagens and implications for immune cell regulation in disease

    Research output: Contribution to journalReviewResearchpeer-review

  4. TAFI deficiency causes maladaptive vascular remodeling after hemophilic joint bleeding

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. CCL2/MCP-1 signaling drives extracellular matrix turnover by diverse macrophage subsets

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

Proteolytic degradation processes, resulting from the activation of plasminogen by the specific enzyme, urokinase plasminogen activator (uPA), take place in the extracellular matrix during cancer invasion as well as in tissue remodelling under certain normal-physiological conditions. The uPA receptor, uPAR, is a cell-surface protein which plays an important role in the localization and regulation of these processes. In the present article a number of established conclusions concerning the structure and function of uPAR are presented, and in addition various models are discussed which might explain additional observations for which the mechanisms involved have not yet been clarified experimentally. uPAR is a highly glycosylated, 3-domain protein, anchored in the plasma membrane by a glycolipid moiety. The domain organization is important for efficient ligand-binding, and the NH2-terminal domain is directly involved in the molecular contact with uPA. The receptor binds uPA as well as its proenzyme, pro-uPA, in such a manner that the activation cascade can occur directly on the cell surface. Furthermore, the activation rates are enhanced relative to the situation in solution, probably due to an interplay between uPAR and other, unidentified components. In addition to the function in the regulation of proteolysis, uPAR seems to play a role in internalization processes and in cellular signal transduction and adhesion. A few reagents have been identified which are capable to inhibit the interaction between uPAR and uPA. The growing knowledge on the structure and function of uPAR which is a result of protein chemical analyses, functional studies and analyses of other, interacting components, should help to obtain a better understanding of the regulation of extracellular proteolysis. In conjunction with the continuous identification of inhibitory reagents, this knowledge should open the possibility to interfere with the resulting, degradative events.

Original languageEnglish
JournalBiological Chemistry Hoppe-Seyler
Issue number5
Pages (from-to)269-79
Number of pages11
Publication statusPublished - May 1995

    Research areas

  • Animals, Humans, Membrane Proteins, Plasminogen Activators, Receptors, Cell Surface, Receptors, Urokinase Plasminogen Activator

ID: 46435143