Abstract
Cofilin, an actin-binding protein, is essential for a variety of cell responses. In this study, we investigated the correlation between proliferation and cofilin phosphorylation in response to platelet-derived growth factor (PDGF) in rat aortic smooth muscle cells (RASMCs). The phosphorylation of cofilin and activity of mitogen-activated protein kinase (MAPK) were measured by Western analyses and proliferation in RASMCs was measured by BrdU incorporation assays. The phosphorylation of cofilin in RASMCs was decreased by PDGF-BB treatment at 10 min, but recovered to the level of the quiescent state at 60 min. PDGF-BB-induced dephosphorylation of cofilin was inhibited by pretreatment with piceatannol (a spleen tyrosine kinase [Syk] inhibitor), PP2 (a Src inhibitor), or SP600125 (a c-Jun N-terminal kinase [JNK] inhibitor), but not by PD98059, an inhibitor of extracellular signal-regulated kinase 1/2. PDGF-BB increased JNK activity and proliferation, and these responses were suppressed by kinase inhibitors and small interference RNA-cofilin. The results suggest that PDGF-BB-induced dephosphorylation of cofilin can be promoted via the JNK pathway, which is regulated by both Syk and Src kinases and that cofilin dephosphorylation may be involved in PDGF-BB-induced RASMC proliferation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Aorta / metabolism
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Becaplermin
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Cell Proliferation* / drug effects
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Cells, Cultured
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Cofilin 2 / genetics
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Cofilin 2 / metabolism*
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Intracellular Signaling Peptides and Proteins / antagonists & inhibitors
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Intracellular Signaling Peptides and Proteins / metabolism
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Male
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Mitogen-Activated Protein Kinases / antagonists & inhibitors
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Mitogen-Activated Protein Kinases / metabolism
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Muscle, Smooth, Vascular / drug effects
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Muscle, Smooth, Vascular / enzymology
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Muscle, Smooth, Vascular / metabolism*
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Myocytes, Smooth Muscle / drug effects
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Myocytes, Smooth Muscle / enzymology
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Myocytes, Smooth Muscle / metabolism*
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Phosphoprotein Phosphatases / antagonists & inhibitors
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Phosphoprotein Phosphatases / metabolism
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Phosphorylation
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Platelet-Derived Growth Factor / metabolism*
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Protein Kinase Inhibitors / pharmacology
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Protein-Tyrosine Kinases / antagonists & inhibitors
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Protein-Tyrosine Kinases / metabolism
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Proto-Oncogene Proteins c-sis
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RNA Interference
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RNA, Small Interfering / metabolism
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Rats
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Rats, Sprague-Dawley
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Syk Kinase
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Time Factors
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src-Family Kinases / antagonists & inhibitors
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src-Family Kinases / metabolism
Substances
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Cofilin 2
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Intracellular Signaling Peptides and Proteins
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Platelet-Derived Growth Factor
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Protein Kinase Inhibitors
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Proto-Oncogene Proteins c-sis
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RNA, Small Interfering
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Becaplermin
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Protein-Tyrosine Kinases
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Syk Kinase
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Syk protein, rat
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src-Family Kinases
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Mitogen-Activated Protein Kinases
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Phosphoprotein Phosphatases