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Urokinase‐induced signaling in human vascular smooth muscle cells is mediated by PDGFR‐β
Author(s) -
Kiyan Julia,
Kiyan Roman,
Haller Hermann,
Dumler Inna
Publication year - 2005
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600669
Subject(s) - biology , vascular smooth muscle , signal transduction , microbiology and biotechnology , urokinase , urokinase receptor , platelet derived growth factor receptor , cancer research , smooth muscle , receptor , endocrinology , biochemistry , genetics , growth factor
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)‐β. The interaction results in PDGF‐independent PDGFR‐β activation by phosphorylation of cytoplasmic tyrosine kinase domains and receptor dimerization. Association of the receptors as well as the tyrosine kinase activity of PDGFR‐β 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.