scholarly journals Cooperativity between the Ras-ERK and Rho-Rho Kinase Pathways in Urokinase-type Plasminogen Activator-stimulated Cell Migration

2002 ◽  
Vol 277 (14) ◽  
pp. 12479-12485 ◽  
Author(s):  
Minji Jo ◽  
Keena S. Thomas ◽  
Avril V. Somlyo ◽  
Andrew P. Somlyo ◽  
Steven L. Gonias
Keyword(s):  
Cell Migration ◽  
Plasminogen Activator ◽  
Rho Kinase ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator

scholarly journals Estramustine Phosphate Inhibits TGF-β-Induced Mouse Macrophage Migration and Urokinase-Type Plasminogen Activator Production

2018 ◽  
Vol 2018 ◽  
pp. 1-10
Author(s):  
Sonja S. Mojsilovic ◽  
Slavko Mojsilovic ◽  
Suncica Bjelica ◽  
Juan F. Santibanez
Keyword(s):  
Cell Migration ◽  
Cell Motility ◽  
Plasminogen Activator ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Raw 264.7 ◽  
Estramustine Phosphate ◽  
Macrophage Cell ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator

Transforming growth factor-beta (TGF-β) has been demonstrated as a key regulator of immune responses including monocyte/macrophage functions. TGF-β regulates macrophage cell migration and polarization, as well as it is shown to modulate macrophage urokinase-type plasminogen activator (uPA) production, which also contributes to macrophage chemotaxis and migration toward damaged or inflamed tissues. Microtubule (MT) cytoskeleton dynamic plays a key role during the cell motility, and any interference on the MT network profoundly affects cell migration. In this study, by using estramustine phosphate (EP), which modifies MT stability, we analysed whether tubulin cytoskeleton contributes to TGF-β-induced macrophage cell migration and uPA expression. We found out that, in the murine macrophage cell line RAW 264.7, EP at noncytotoxic concentrations inhibited cell migration and uPA expression induced by TGF-β. Moreover, EP greatly reduced the capacity of TGF-β to trigger the phosphorylation and activation of its downstream Smad3 effector. Furthermore, Smad3 activation seems to be critical for the increased cell motility. Thus, our data suggest that EP, by interfering with MT dynamics, inhibits TGF-β-induced RAW 264.7 cell migration paralleled with reduction of uPA induction, in part by disabling Smad3 activation by TGF-β.

scholarly journals GPI-anchored uPAR requires Endo180 for rapid directional sensing during chemotaxis

2003 ◽  
Vol 162 (5) ◽  
pp. 789-794 ◽  
Author(s):  
Justin Sturge ◽  
Dirk Wienke ◽  
Lucy East ◽  
Gareth E. Jones ◽  
Clare M. Isacke
Keyword(s):  
Plasma Membrane ◽  
Cell Migration ◽  
Plasminogen Activator ◽  
Specific Function ◽  
Receptor Endocytosis ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Trimolecular Complex ◽  
Rapid Activation ◽  
Cell Chemotaxis

Urokinase-type plasminogen activator (uPA) and its receptor (uPAR) play an important role in cell guidance and chemotaxis during normal and pathological events. uPAR is GPI-anchored and the mechanism by which it transmits intracellular polarity cues across the plasma membrane during directional sensing has not been elucidated. The constitutively recycling endocytic receptor Endo180 forms a trimolecular complex with uPAR in the presence of uPA, hence its alternate name uPAR-associated protein. Here, we demonstrate that Endo180 is a general promoter of random cell migration and has a more specific function in cell chemotaxis up a uPA gradient. Endo180 expression was demonstrated to enhance uPA-mediated filopodia production and promote rapid activation of Cdc42 and Rac. Expression of a noninternalizing Endo180 mutant revealed that promotion of random cell migration requires receptor endocytosis, whereas the chemotactic response to uPA does not. From these studies, we conclude that Endo180 is a crucial link between uPA–uPAR and setting of the internal cellular compass.

scholarly journals Structure-based design of an urokinase-type plasminogen activator receptor–derived peptide inhibiting cell migration and lung metastasis

2009 ◽  
Vol 8 (9) ◽  
pp. 2708-2717 ◽  
Author(s):  
Maria Vincenza Carriero ◽  
Immacolata Longanesi-Cattani ◽  
Katia Bifulco ◽  
Ornella Maglio ◽  
Liliana Lista ◽  
...  
Keyword(s):  
Cell Migration ◽  
Plasminogen Activator ◽  
Lung Metastasis ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Plasminogen Activator Receptor
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