Urokinase-induced signaling in human vascular smooth muscle cells is mediated by PDGFR-beta

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Item Type:	Article
Title:	Urokinase-induced signaling in human vascular smooth muscle cells is mediated by PDGFR-beta
Creators Name:	Kiyan, J., Kiyan, R., Haller, H. and Dumler, I.
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)-{beta}. The interaction results in PDGF-independent PDGFR-{beta} activation by phosphorylation of cytoplasmic tyrosine kinase domains and receptor dimerization. Association of the receptors as well as the tyrosine kinase activity of PDGFR-{beta} 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
Source:	EMBO Journal
ISSN:	0261-4189
Publisher:	Nature Publishing Group
Volume:	24
Number:	10
Page Range:	1787-1797
Date:	18 May 2005
Official Publication:	https://doi.org/10.1038/sj.emboj.7600669
PubMed:	View item in PubMed

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