| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,1
* Pulmonary Cell Research, and
Cardiovascular Research-Signal Transduction, Department of Research, University Hospital Basel, Basel, Switzerland; and
The Woolcock Institute for Medical Research, Camperdown, Australia
1Correspondence: Pulmonary Cell Research, Department of Research, Basel University Hospital, Hebelstrasse 20, CH-4031 Basel, Switzerland. E-mail: michelr{at}med.usyd.edu.au
Urokinase and its receptor uPAR play a role in cell migration that is being actively characterized. We previously reported that urokinase potentiates cell migration in human airway smooth muscle cells only where there is some primary migratory stimulus such as PDGF or recent exposure to growth medium. In this study, we examined the signaling of urokinase through its receptor, which lacks an intracellular domain and is presumed to act through associations with other membrane proteins. Whereas PDGF (30 min) and PDGF with urokinase increased the amount of the tyrosine dephosphorylase SHP2 in the membrane fraction, urokinase alone (30 min) decreased membrane SHP2. Analysis of the time course of urokinase stimulation showed that SHP2 was brought into association with the urokinase receptor uPAR between 2.5 and 20 min of urokinase, and later dissociated from it. Focal adhesion kinase was steadily lost from association with uPAR during urokinase stimulation, but its phosphorylation state increased and it became cleaved to smaller molecules. Association of uPAR with caveolin also decreased during urokinase stimulation. In contrast, the tyrosine kinase Src increased in the membrane fraction in response to urokinase stimulation. Disruption of raft structures by cyclodextrin treatment led to potentiation of PDGF chemotaxis, similar to urokinase action. Blocking of dephosphorylase activity with vanadate reduced basal cell migration and blocked the action of urokinase on PDGF chemotaxis. These observations support a role for urokinase in altering the phosphorylation state of focal adhesions, leading to breakdown of their structure and facilitation of cell motility.—Carlin, S. M., Resink, T. J., Tamm, M., Roth, M. Urokinase signal transduction and its role in cell migration.
Key Words: uPAR • signaling • FAK • SHP2 • cell migration
This article has been cited by other articles:
|
|
 |
|
  W. T. Gerthoffer Migration of Airway Smooth Muscle Cells Proceedings of the ATS, January 1, 2008; 5(1): 97 - 105. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. C. Bryer and T. J. Koh The urokinase-type plasminogen activator receptor is not required for skeletal muscle inflammation or regeneration Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2007; 293(3): R1152 - R1158. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Shetty, T. Velusamy, S. Idell, H. Tang, and P. K. Shetty Regulation of urokinase receptor expression by protein tyrosine phosphatases Am J Physiol Lung Cell Mol Physiol, February 1, 2007; 292(2): L414 - L421. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Maquerlot, S. Galiacy, M. Malo, C. Guignabert, D. A. Lawrence, M.-P. d'Ortho, and G. Barlovatz-Meimon Dual Role for Plasminogen Activator Inhibitor Type 1 as Soluble and as Matricellular Regulator of Epithelial Alveolar Cell Wound Healing Am. J. Pathol., November 1, 2006; 169(5): 1624 - 1632. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. D. Hardin and J. Vallejo Caveolins in vascular smooth muscle: Form organizing function Cardiovasc Res, March 1, 2006; 69(4): 808 - 815. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Pulukuri, C. S. Gondi, S. S. Lakka, A. Jutla, N. Estes, M. Gujrati, and J. S. Rao RNA Interference-directed Knockdown of Urokinase Plasminogen Activator and Urokinase Plasminogen Activator Receptor Inhibits Prostate Cancer Cell Invasion, Survival, and Tumorigenicity in Vivo J. Biol. Chem., October 28, 2005; 280(43): 36529 - 36540. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
