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

Official URL:https://doi.org/10.1038/sj.emboj.7600669
PubMed:View item in PubMed
Creators Name:Kiyan, J. and Kiyan, R. and Haller, H. and Dumler, I.
Journal Title:EMBO Journal
Journal Abbreviation:EMBO J
Volume:24
Number:10
Page Range:1787-1797
Date:18 May 2005
Keywords:Migration, Platelet-Derived Growth Factor Receptor, Proliferation, Urokinase Receptor, Vascular Smooth Muscle Cells
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.
ISSN:0261-4189
Publisher:Nature Publishing Group (U.S.A.)
Item Type:Article

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