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

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.

SUBMITTER: Kiyan J

PROVIDER: S-EPMC1142599 | biostudies-literature | 2005 May

REPOSITORIES: biostudies-literature

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

Kiyan Julia J Kiyan Roman R Haller Hermann H Dumler Inna I

The EMBO journal 20050505 10

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 cytoplasm ...[more]

PMID: 15889147

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