Cofilin phosphorylation mediates proliferation in response to platelet-derived growth factor-BB in rat aortic smooth muscle cells.
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.
Won
Kyung-Jong
KJ
Institute of Medical Sciences, School of Medicine, Konkuk University, Chungju, Korea.
Park
Seung Hwa
SH
Park
Taekyu
T
Lee
Chang-Kwon
CK
Lee
Hwan Myung
HM
Choi
Wahn Soo
WS
Kim
Sun-Jong
SJ
Park
Pyo-Jam
PJ
Jang
Hyung-Kwan
HK
Kim
Soon Heum
SH
Kim
Bokyung
B
D000818:Animals; D001011:Aorta / Q000378:metabolism; D000077214:Becaplermin; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D051340:Cofilin 2 / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000072377:Syk Kinase; D013997:Time Factors; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D051340:Cofilin 2; D047908:Intracellular Signaling Peptides and Proteins; D010982:Platelet-Derived Growth Factor; D047428:Protein Kinase Inhibitors; D020574:Proto-Oncogene Proteins c-sis; D034741:RNA, Small Interfering; D000077214:Becaplermin; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606898:Syk protein, rat; D019061:src-Family Kinases; D020928:Mitogen-Activated Protein Kinases; D010749:Phosphoprotein Phosphatases