Syndecan-4 regulates platelet-derived growth factor-mediated MAP kinase activation by altering intracellular reactive oxygen species.
The cell adhesion receptor, syndecan-4, regulates cellular interactions with both the extracellular matrix and soluble ligands. Accumulating evidence also suggests that cell adhesion is involved in generating reactive oxygen species (ROS). Here, we investigated the role of syndecan-4 in regulating growth factor-induced ROS generation. Rat embryo fibroblasts (REFs) overexpressing syndecan-4 exhibited increased ROS levels compared to control cells. Expression of the non-phagocytic NADH oxidase component Nox1 was increased in syndecan-4-overexpressing REFs and syndecan-4-mediated ROS generation was diminished when levels of Nox1 were knocked-down with small inhibitory RNAs. In addition, syndecan-4 enhanced platelet-derived growth factor (PDGF)-induced MAP kinase activity in parallel with ROS generation. Collectively, these data suggest that syndecan-4 regulates PDGF-induced MAP kinase activation by altering ROS generation.
Kim
Jungyean
J
Department of Life Sciences, Division of Life and Pharmaceutical Sciences and the Center for Cell Signaling and Drug Discovery Research, Ewha Womans University, Daehyun-dong, Seodaemoon-Gu, Seoul 120-750, Republic of Korea.
Lee
Jung-hyun
JH
Park
Hey Sun
HS
Hwang
Jisun
J
Han
Inn-Oc
IO
Bae
Yun Soo
YS
Oh
Eok-Soo
ES
D000818:Animals; D002460:Cell Line; D004789:Enzyme Activation; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D053671:Syndecan-4 / Q000235:genetics / Q000378:metabolism*
D010982:Platelet-Derived Growth Factor; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D053671:Syndecan-4; D019255:NADPH Oxidases; D020929:Mitogen-Activated Protein Kinase Kinases