Spleen tyrosine kinase participates in Src-mediated migration and proliferation by PDGF-BB in rat aortic smooth muscle cells.
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 microM) and piceatannol (30 microM), inhibitors of Src and Syk, respectively. The phosphorylation of Syk induced by PDGF-BB was abolished by PP2. PDGF-BB increased the co-association of the PDGFbeta-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 microM) and PD98059 (30 microM), 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.
Lee
Hwan Myung
HM
Department of Medicine, College of Medicine, Konkuk University, Chungju 380-701, Korea.
Kim
Hyo Jin
HJ
Park
Hyo-Jun
HJ
Won
Kyung-Jong
KJ
Kim
Junghwan
J
Shin
Hwa-Sup
HS
Park
Pyo-Jam
PJ
Kim
Hyun-Jun
HJ
Lee
Kyung-Yung
KY
Park
Seung Hwa
SH
Lee
Chang-Kwon
CK
Kim
Bokyung
B
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects; D000077214:Becaplermin; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D015194:Diffusion Chambers, Culture; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D016391:Genes, src / Q000502:physiology*; D007093:Imidazoles / Q000494:pharmacology; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D020928:Mitogen-Activated Protein Kinases; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D020574:Proto-Oncogene Proteins c-sis; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017479:Receptors, Platelet-Derived Growth Factor / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013154:Spleen / Q000201:enzymology*; D014945:Wound Healing / Q000502:physiology
D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011725:Pyridines; D000077214:Becaplermin; D011505:Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor; D020928:Mitogen-Activated Protein Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one