Angiogenesis: A Paradigm for Balanced Extracellular Proteolysis during Cell Migration and Morphogenesis

1996 ◽  
Vol 49 (1-3) ◽  
pp. 138-162 ◽  
Author(s):  
Michael S. Pepper ◽  
Roberto Montesano ◽  
Stefano J. Mandriota ◽  
Lelio Orci ◽  
Jean-Dominique Vassalli
Keyword(s):  
Cell Migration ◽  
Extracellular Proteolysis

scholarly journals Alpha-2-Macroglobulin in Inflammation, Immunity and Infections

2021 ◽  
Vol 12 ◽  
Author(s):  
Jennifer Vandooren ◽  
Yoshifumi Itoh
Keyword(s):  
Cell Migration ◽  
Growth Factors ◽  
Protease Inhibitor ◽  
Broad Spectrum ◽  
Cell Function ◽  
Immune Cell ◽  
Extracellular Proteins ◽  
Immune Cell Function ◽  
Extracellular Proteolysis

Alpha-2-macroglobulin is an extracellular macromolecule mainly known for its role as a broad-spectrum protease inhibitor. By presenting itself as an optimal substrate for endopeptidases of all catalytic types, alpha-2-macroglobulin lures active proteases into its molecular cage and subsequently ‘flags’ their complex for elimination. In addition to its role as a regulator of extracellular proteolysis, alpha-2-macroglobulin also has other functions such as switching proteolysis towards small substrates, facilitating cell migration and the binding of cytokines, growth factors and damaged extracellular proteins. These functions appear particularly important in the context of immune-cell function. In this review manuscript, we provide an overview of all functions of alpha-2-macroglobulin and place these in the context of inflammation, immunity and infections.

The urokinase plasminogen activator and its receptor

2005 ◽  
Vol 93 (02) ◽  
pp. 205-211 ◽  
Author(s):  
Daniela Alfano ◽  
Paola Franco ◽  
Immacolata Vocca ◽  
Nadia Gambi ◽  
Viviana Pisa ◽  
...  
Keyword(s):  
Cell Migration ◽  
Plasminogen Activator ◽  
Cancer Metastasis ◽  
Dynamic Control ◽  
Migration And Invasion ◽  
Cell Matrix ◽  
Pathological Conditions ◽  
Type Plasminogen Activator ◽  
Apoptosis Ratio ◽  
Extracellular Proteolysis

SummaryThe urinary-type plasminogen activator, or uPA, controls matrix degradation through the conversion of plasminogen into plasmin and is regarded as the critical trigger for plasmin generation during cell migration and invasion, under physiological and pathological conditions (such as cancer metastasis).The proteolytic activity of uPA is responsible for the activation or release of several growth factors and modulates the cell survival/apoptosis ratio through the dynamic control of cell-matrix contacts. The urokinase receptor (uPAR), binding to the EGF-like domain of uPA, directs membrane-associated extracellular proteolysis and signals through transmembrane proteins, thus regulating cell migration, adhesion and cytoskeletal status. However, recent evidence highlights an intricate relationship linking the uPA/uPAR system to cell growth and apoptosis.

scholarly journals A cellular binding site for the Mr 55,000 form of the human plasminogen activator, urokinase.

1985 ◽  
Vol 100 (1) ◽  
pp. 86-92 ◽  
Author(s):  
J D Vassalli ◽  
D Baccino ◽  
D Belin
Keyword(s):  
Cell Migration ◽  
Plasminogen Activator ◽  
Plasminogen Activators ◽  
Plasminogen Activation ◽  
Blood Monocytes ◽  
High Affinity ◽  
Human Plasminogen ◽  
A Chain ◽  
Optimal Site ◽  
Extracellular Proteolysis

The secretion of plasminogen activators has been implicated in the controlled extracellular proteolysis that accompanies cell migration and tissue remodeling. We found that the human plasminogen activator urokinase (Uk) (Mr 55,000 form) binds rapidly, specifically, and with high affinity to fresh human blood monocytes and to cells of the monocyte line U937. Upon binding Mr 55,000 Uk was observed to confer high plasminogen activator activity to the cells. Binding of the enzyme did not require a functional catalytic site (located on the B chain of the protein) but did require the noncatalytic A chain of Mr 55,000 Uk, since Mr 33,000 Uk did not bind. These results demonstrate the presence of a membrane receptor for Uk on monocytes and show a hitherto unknown function for the A chain of Uk: binding of secreted enzyme to its receptor results in Uk acting as a membrane protease. This localizes plasminogen activation near the cell surface, an optimal site to facilitate cell migration.

scholarly journals Upregulation of urokinase receptor expression on migrating endothelial cells

1993 ◽  
Vol 122 (3) ◽  
pp. 673-684 ◽  
Author(s):  
MS Pepper ◽  
AP Sappino ◽  
R Stöcklin ◽  
R Montesano ◽  
L Orci ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Migration ◽  
Endothelial Cell ◽  
Cell Monolayer ◽  
Receptor Expression ◽  
Endothelial Cell Migration ◽  
Extracellular Proteolysis ◽  
Migrating Cells

One of the phenotypic hallmarks of migrating endothelial cells, both in vivo and in vitro, is expression of the urokinase-type plasminogen activator (u-PA), a key mediator of extracellular proteolysis. In the study reported here, we have used an in vitro model of endothelial cell migration to explore the mechanism of this phenomenon. We have found that wounding of an endothelial cell monolayer triggers a marked, rapid and sustained increase in expression of a specific high-affinity receptor for u-PA (u-PAr) on the surface of migrating cells. Migrating cells displayed an increase in the levels of u-PA and u-PAr mRNAs, and this increase was mediated by endogenous basic fibroblast growth factor (bFGF). We also show that the increase in u-PA activity on migrating cells can be accounted for by an increase in receptor-bound u-PA, and that the increase in activity is also dependent on endogenous bFGF. These results demonstrate that the expression of plasmin-mediated proteolytic activity by migrating endothelial cells is a consequence of increased production of both u-PA and its receptor, and that this in turn is mediated by endogenous bFGF. This suggests that u-PA, produced at increased levels by migrating cells, binds to u-PAr whose expression is upregulated on the same cells. These observations are in accord with the postulated role of u-PAr in mediating efficient and spatially restricted extracellular proteolysis, particularly in the context of cell migration.

Neutrophil migration through in vitro interstitial matrix

1992 ◽  
Vol 50 (1) ◽  
pp. 894-895
Author(s):  
J. Roemer ◽  
S.R. Simon
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Cell Migration ◽  
Smooth Muscle Cells ◽  
Inflammatory Cell ◽  
Neutrophil Migration ◽  
Culture Conditions ◽  
Aortic Smooth Muscle ◽  
Specific Culture

We are developing an in vitro interstitial extracellular matrix (ECM) system for study of inflammatory cell migration. Falcon brand Cyclopore membrane inserts of various pore sizes are used as a support substrate for production of ECM by R22 rat aortic smooth muscle cells. Under specific culture conditions these cells produce a highly insoluble matrix consisting of typical interstitial ECM components, i.e.: types I and III collagen, elastin, proteoglycans and fibronectin.

The role of DUBs in the post-translational control of cell migration

2019 ◽  
Vol 63 (5) ◽  
pp. 579-594 ◽  
Author(s):  
Guillem Lambies ◽  
Antonio García de Herreros ◽  
Víctor M. Díaz
Keyword(s):  
Cell Migration ◽  
Translational Control ◽  
Epithelial To Mesenchymal Transition ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Mesenchymal Transition ◽  
Tgfβ Receptors ◽  
Fundamental Process ◽  
Multistep Process

Abstract Cell migration is a multifactorial/multistep process that requires the concerted action of growth and transcriptional factors, motor proteins, extracellular matrix remodeling and proteases. In this review, we focus on the role of transcription factors modulating Epithelial-to-Mesenchymal Transition (EMT-TFs), a fundamental process supporting both physiological and pathological cell migration. These EMT-TFs (Snail1/2, Twist1/2 and Zeb1/2) are labile proteins which should be stabilized to initiate EMT and provide full migratory and invasive properties. We present here a family of enzymes, the deubiquitinases (DUBs) which have a crucial role in counteracting polyubiquitination and proteasomal degradation of EMT-TFs after their induction by TGFβ, inflammatory cytokines and hypoxia. We also describe the DUBs promoting the stabilization of Smads, TGFβ receptors and other key proteins involved in transduction pathways controlling EMT.

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