Tyk2 mediates effects of urokinase on human vascular smooth muscle cell growth.
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Tyk2 mediates effects of urokinase on human vascular smooth muscle cell growth. / Patecki, Margret; von Schaewen, Markus; Tkachuk, Sergey; Jerke, Uwe; Dietz, Rainer; Dumler, Inna; Kusch, Angelika.
In: BIOCHEM BIOPH RES CO, Vol. 359, No. 3, 3, 2007, p. 679-684.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Tyk2 mediates effects of urokinase on human vascular smooth muscle cell growth.
AU - Patecki, Margret
AU - von Schaewen, Markus
AU - Tkachuk, Sergey
AU - Jerke, Uwe
AU - Dietz, Rainer
AU - Dumler, Inna
AU - Kusch, Angelika
PY - 2007
Y1 - 2007
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 359
SP - 679
EP - 684
JO - BIOCHEM BIOPH RES CO
JF - BIOCHEM BIOPH RES CO
SN - 0006-291X
IS - 3
M1 - 3
ER -
