gms | German Medical Science

28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

24. bis 27.11.2004, Hannover

uPA-induced signaling, migration and proliferation are mediated by PDGFR

uPA induzierte Signaltransdukzion, Migration and Proliferation werden in numanen vaskulären Glattmuskelzellen durch PDGFR vermittelt

Meeting Abstract (Hypertonie 2004)

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  • I. Kilian - Medizinische Hochschule Hannover (Hannover, D)
  • H. Haller - Medizinische Hochschule Hannover (Hannover, D)
  • I. Dumler - Medizinische Hochschule Hannover (Hannover, D)

Hypertonie 2004. 28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Hannover, 24.-27.11.2004. Düsseldorf, Köln: German Medical Science; 2005. Doc04hochP30

The electronic version of this article is the complete one and can be found online at:

Published: August 10, 2005

© 2005 Kilian et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Vascular smooth muscle cells (VSMC) play a fundamental role in hypertension-associated vascular remodelling due to increased cell growth, cell migration, extracellular matrix deposition and inflammation. Urokinase-type plasminogen activator (uPA) and its receptor (uPAR) not only serve to localize proteolysis on cell surface, but also induce cellular responses towards cell migration, adhesion and proliferation in a non-proteolytic fashion. We demonstrated recently that the uPAR-Tyk2-PI3-K-RhoA-Rho kinase pathway mediates uPA-induced VSMC migration, whereas uPA-dependent changes of VSMC proliferation are mediated by STAT1. However, since uPAR is a GPI-anchored protein and lacks any transmembrane domain, it remained unknown how these two cascades are linked to uPAR. Here we provide evidence that in VSMC platelet-derived growth factor receptor (PDGFRß) serves as a transmembrane adaptor for uPAR.

We demonstrate that PDGFR tyrosine kinase activity is required for uPA to promote both, promigratory and profilerative effects. Thus, inhibition of PDGFR tyrosine kinase activity with either specific inhibitor AG 1295 or by overexpression of tyrosine kinase inactive PDGFR mutant prevented uPA-induced VSMC migration and proliferation. Further, we demonstrate by co-immunoprecipitation approach that uPAR and PDGFR in VSMC are associated in a uPA-dependent manner. Furthermore, we observed increased uPAR- and time-dependent PDGFR autophosphorylation in response to uPA stimulation in VSMC in the absence of PDGF. Tyrosine kinase activity of PDGFR is also required for the uPA-induced RhoA activation, and STAT1 tyrosine phosphorylation, since its inhibition by either pharmacological inhibitor or by overexpression of tyrosine kinase inactive PDGFR mutant abolished uPA-induced responses.

Taken together, these findings suggest that PDGFR is involved in regulation of uPA-induced signaling and functional behaviour of human VSMC and can serve as a transmembrane adaptor of uPAR.