Taurine suppresses platelet-derived growth factor (PDGF) BB-induced PDGF-beta receptor phosphorylation by protein tyrosine phosphatase-mediated dephosphorylation in vascular smooth muscle cells.
In atherosclerosis, abnormal vascular smooth muscle cell (VSMC) proliferation plays an important role to form fibroproliferative lesions and platelet-derived growth factor (PDGF)-BB is one of the most potent chemoattractants and proliferative factors for VSMCs. Taurine, sulfur-containing beta-amino acid, has been considered to prevent the development of atherosclerosis, although the molecular mechanism remains obscure. Previously, we demonstrated that taurine significantly suppressed PDGF-BB-induced cell proliferation, DNA synthesis, immediate-early gene expressions and extracellular signal-regulated kinase (ERK) 1/2 phosphorylation in VSMCs. The present study was aimed at elucidating the precise molecular mechanism of taurine in PDGF-BB signaling pathway. We showed that taurine significantly suppressed PDGF-BB-induced phosphorylation of PDGF-beta receptor and activation of its downstream signaling molecules such as Ras, MAPK/ERK kinase (MEK)1/2 and Akt. Because taurine did not attenuate phorbol 12-myristate 13-acetate (PMA)-induced PDGF-beta receptor-independent ERK1/2 phosphorylation, we further investigated the suppressive mechanism of taurine in PDGF-beta receptor level. Although taurine did not directly affect PDGF receptor autophosphorylation in vitro, taurine promoted PDGF-beta receptor dephosphorylation and restored PDGF-BB-induced suppression of protein tyrosine phosphatase (PTPase) activity. Taken together, we propose that taurine could prevent or delay the progression of atherosclerosis by PTPase-mediated suppression of PDGF-beta receptor phosphorylation, and by decreasing the activation of its downstream signaling molecules in VSMCs.
Yoshimura
Hitoshi
H
Department of Biochemistry and Molecular Medicine, Shimane University Faculty of Medicine, Izumo 693-8501, Japan.
Nariai
Yuko
Y
Terashima
Masaharu
M
Mitani
Toshifumi
T
Tanigawa
Yoshinori
Y
D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism*; D000077214:Becaplermin; D015153:Blotting, Western; D006801:Humans; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D011921:Rats, Inbred WKY; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013654:Taurine / Q000494:pharmacology*
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D013654:Taurine; D020797:Receptor, Platelet-Derived Growth Factor beta; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D017027:Protein Tyrosine Phosphatases