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

Authors:
Kiyan J, Kiyan R, Haller H and Dumler I
In:
Source: EMBO J
Publication Date: (2005)
Issue: 24(10): 1787-1797
Research Area:
Cardiovascular
Cells used in publication:
SMC, coronary artery, human (CASMC)
Species: human
Tissue Origin: artery
Platform:
Nucleofectorâ„¢ I/II/2b
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