Urokinase-induced Signaling in Human Vascular Smooth Muscle Cells is Mediated by PDGFR-beta

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2005 May 13

PMID 15889147

Citations 33

Authors

Julia Kiyan

Roman Kiyan

Hermann Haller

Inna Dumler

Affiliations

Soon will be listed here.

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.

Citing Articles

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suPAR: An Inflammatory Mediator for Kidneys.

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