Plasminogen activation at the cell surface

Ellis, Vincent (2003) Plasminogen activation at the cell surface. Current Topics in Developmental Biology, 54. pp. 263-312.

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Abstract

It has been emphasized here that plasminogen represents an enormous reservoir of proteolytic potential and that its activation is consequently a highly regulated process. This begins at the level of transcriptional regulation of the two plasmino-gen activators and in some cell types also their regulated secretion. However, the functional regulation of the plasminogen activators is the level at which the com-plexity of this proteolytic system is most apparent. It is now clear that a diversity of mechanisms exist to regulate the activation and activity of the plasminogen activa-tors, and that these include the utilization of these soluble proteins as cell-surface proteases. uPA is clearly the primary plasminogen activator in this context, binding uPAR and forming catalytic complexes that generate plasmin activity with very high efficiency, and furthermore cooperating with protease inhibitors to confine this ac-tivity to the cell surface or pericellular environment. The activity of this proteolytic system, which is thought to be involved in mediating invasive cellular migration, appears to be functionally linked to other systems fundamental to this cellular behavior. A variety of mechanisms have been proposed, but a common feature is direct or indirect interactions with integrins potentially leading to signaling to the cellular cytoskeletal machinery, suggesting a cooperativity between these systems in mediating invasive migration. tPA clearly also has the potential to act as a cell-surface protease, in addition to its fibrin-dependent role in vascular hemostasis. A variety of cellular binding sites for tPA have been identified, some of which appear to regulate plasminogen activation as efficiently as uPAR. In contrast to uPAR, these binding sites may be cell-type specific, although their roles in vivo have yet to be established.

Item Type:	Article
Faculty \ School:	Faculty of Science > School of Biological Sciences
UEA Research Groups:	Faculty of Science > Research Groups > Cells and Tissues
Depositing User:	EPrints Services
Date Deposited:	01 Oct 2010 13:37
Last Modified:	22 Apr 2023 01:59
URI:	https://ueaeprints.uea.ac.uk/id/eprint/715
DOI:	10.1016/S0070-2153(03)54012-1

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