Article
- The EMBO Journal (2005) 24, 1787 - 1797
- doi:10.1038/sj.emboj.7600669
Published online: 5 May 2005
Subject Category:
Urokinase-induced signaling in human vascular smooth muscle cells is mediated by PDGFR-
Julia Kiyan1, Roman Kiyan1, Hermann Haller1 and Inna Dumler1,2
- Hannover Medical School, Hannover, Germany
- Medical Faculty of the Charité, Franz Volhard Klinik, HELIOS Klinikum-Berlin, Max Delbrück Center, Berlin, Germany
Correspondence to:
Julia Kiyan,
Nephrology Department, Hannover Medical School, Carl-Neuberg Stra
e 1, D-30625 Hannover, Germany. Tel.: +49 511 532 2719; Fax: +49 511 532 2713; E-mail: kiian.ioulia@mh-hannover.de
Received 22 October 2004; Accepted 31 March 2005
Abstract
Urokinase (uPA)-induced signaling in human vascular smooth muscle cells (VSMC) elicits important cellular functional responses, such as cell migration and proliferation. However, how intracellular signaling is linked to glycolipid-anchored uPA receptor (uPAR) is unknown. We provide evidence that uPAR activation by uPA induces its association with platelet-derived growth factor receptor (PDGFR)-
. The interaction results in PDGF-independent PDGFR- activation by phosphorylation of cytoplasmic tyrosine kinase domains and receptor dimerization. Association of the receptors as well as the tyrosine kinase activity of PDGFR- are decisive in mediating uPA-induced downstream signaling that regulates VSMC migration and proliferation. These findings provide a molecular basis for mechanisms VSMC use to induce uPAR- and PDGFR-directed signaling. The processes may be relevant to VSMC function and vascular remodeling.
Keywords:
- migration,
- platelet-derived growth factor receptor,
- proliferation,
- urokinase receptor,
- vascular smooth muscle cells
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated
RESEARCH
The uPA/uPAR system regulates the bioavailability of PDGF-DD: implications for tumour growth
Oncogene Original Article
The EMBO Journal Article (17 Nov 2003)
The EMBO Journal Article (17 Nov 2003)
