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KMID : 0043320070300060761
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Archives of Pharmacal Research
2007 Volume.30 No. 6 p.761 ~ p.769
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Spleen Tyrosine Kinase Participates in Src-Mediated Migration and Proliferation by PDGF-BB in Rat Aortic Smooth Muscle Cells
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Lee Hwan-Myung
Kim Hyo-Jin
Park Hyo-Jun
Won Kyung-Jong
Kim Jung-Hwan
Shin Hwa-Sup
Park Pyo-Jam
Lee Kyung-Yung
Park Seung-Hwa
Kim Hyun-Jun
Lee Chang-Kwon
Kim Bo-Kyung
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Abstract
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Tyrosine kinases, Src and spleen tyrosine kinase (Syk), play crucial roles in cell responses to platelet-derived growth factor (PDGF) and may have their functional interactions. In this study, we focused on investigating the roles of Syk in the regulation of Src signaling in PDGF-mediated vascular cell responses. Migration, proliferation, and activity of kinases were determined in rat aortic smooth muscle cells (RASMCs). PDGF-BB (10 ng/mL) induced the migration and proliferation of RASMCs, which were significantly inhibited by PP2 (10 μM) and piceatannol (30 μM), inhibitors of Src and Syk, respectively. The phosphorylation of Syk induced by PDGFBB was abolished by PP2. PDGF-BB increased the co-association of the PDGFβ-receptor and the kinases, Src or Syk, and its maximal binding to Src was achieved in a shorter time than that to Syk. PDGF-BB stimulated the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) 1/2, which was inhibited by PP2 and piceatannol. PDGF-BB-induced proliferation and migration were inhibited by SB203580 (30 μM) and PD98059 (30 μM), inhibitors of p38 MAPK and ERK1/2, respectively. These results imply that Syk is regulated by Src kinase, which participates in migration and proliferation in response to PDGF-BB in RASMCs.
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KEYWORD
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Src, Syk, Proliferation, Migration, RASMC
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