Plasminogen activation on the cell surface.
The plasminogen activation system appears to be widely involved in many biological processes in health and disease, but the regulation of plasmin generation or the mechanisms of stimulation by cell surface receptors are not well understood. Cell surface plasminogen activation requires binding sites for plasminogen substrate and activator enzyme before enhancement of plasmin generation rate is observed. The cell surface moieties involved in binding these reactants appear to be a mixed group of proteins and other molecules, many of which have been extensively investigated. The binding of plasminogen in particular is characterized by heterogeneous receptor molecules, present in high number but generally with low affinity for plasminogen. The low affinity of the interaction, with Kd values around 10(-6) M, presents considerable technical difficulties when studying and quantitating plasminogen binding to cells or isolated receptors. Studying plasminogen activation kinetics in the presence of cells also presents technical difficulties and raises difficult questions on interpretation of results. However, approaches developed to study enzyme activation systems in other areas of hemostasis may also be applied to the problems associated with pericellular proteolysis. Models should be developed that match In vitro experimental data and help us understand the meaning of kinetic constants derived from these systems. In this way it should be possible to better understand the regulation of plasminogen activation around the cell under normal conditions and in a variety of disease states where cell-associated plasminogen activation is believed to be up-regulated. Ultimately, a sound understanding of theses regulatory mechanisms will enable us to devise strategies for modulating proteolytic activity, test these approaches in well designed In vitro systems and relate these results to the in vivo situation.
Longstaff
Colin
C
Division of Haematology, National Institute for Biological Standards and Control, South Mimms, Herts UK, EN6 3QG. clongstaff@nibsc.ac.uk
D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D004789:Enzyme Activation; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D010958:Plasminogen / Q000737:chemistry / Q000378:metabolism*
D008565:Membrane Proteins; D010958:Plasminogen