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Tyk2 mediates effects of urokinase on human vascular smooth muscle cell growth

Item Type:Article
Title:Tyk2 mediates effects of urokinase on human vascular smooth muscle cell growth
Creators Name:Patecki, M. and Schaewen, M.V. and Tkachuk, S. and Jerke, U. and Dietz, R. and Dumler, I. and Kusch, A.
Abstract:The urokinase (uPA)/uPA receptor (uPAR) system plays a role in the response of the vessel wall to injury, presumably by modulating vascular smooth muscle cell (VSMC) functional behaviour. The Jak/Stat signaling pathway has been implicated to mediate the uPA/uPAR-directed cell migration and proliferation in VSMC. We have therefore investigated the underlying molecular mechanisms, which remained not completely understood. In particular, we aimed at identification of the kinase involved in the signaling cascade leading to Stat1 phosphorylation by uPA and its impact on VSMC growth. We performed expression in VSMC of kinase-deficient mutant forms of the Janus kinases Jak1 and Tyk2 and used different cell culture models imitating the response to vascular injury. We provide evidence that Tyk2, but not Jak1, mediates uPA-induced Stat1 phosphorylation and VSMC growth inhibition and suggest a novel function for Tyk2 as an important modulator of the uPA-directed VSMC functional behaviour at the place of injury.
Keywords:Cell proliferation, Co-culture, Jak/Stat pathway, Urokinase/urokinase receptor
Source:Biochemical and Biophysical Research Communications
Publisher:Academic Press
Page Range:679-684
Date:3 August 2007
Official Publication:https://doi.org/10.1016/j.bbrc.2007.05.166
PubMed:View item in PubMed

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