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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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

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.[1]


  1. Urokinase-induced signaling in human vascular smooth muscle cells is mediated by PDGFR-beta. Kiyan, J., Kiyan, R., Haller, H., Dumler, I. EMBO J. (2005) [Pubmed]
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