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.
Kiyan
Julia
J
Nephrology Department, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany. kiian.ioulia@mh-hannover.de
Kiyan
Roman
R
Haller
Hermann
H
Dumler
Inna
I
D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D019281:Dimerization; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D010766:Phosphorylation; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism*; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D004268:DNA-Binding Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D020797:Receptor, Platelet-Derived Growth Factor beta; D014568:Urokinase-Type Plasminogen Activator; D020742:rhoA GTP-Binding Protein