G beta gamma mediate differentiation of vascular smooth muscle cells

Citation
Hp. Reusch et al., G beta gamma mediate differentiation of vascular smooth muscle cells, J BIOL CHEM, 276(22), 2001, pp. 19540-19547
Citations number
53
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
0021-9258 → ACNP
Volume
276
Issue
22
Year of publication
2001
Pages
19540 - 19547
Database
ISI
SICI code
0021-9258(20010601)276:22<19540:GBGMDO>2.0.ZU;2-D
Abstract
Proliferation and subsequent dedifferentiation of vascular smooth muscle (V SM) cells contribute to the pathogenesis of atherosclerosis and postangiopl astic restenosis, The dedifferentiation of VSRI cells in vivo or in cell cu lture is characterized by a loss of contractile proteins such as smooth mus cle-specific Lu-actin and myosin heavy chain (SM-MHC). Serum increased the expression of contractile proteins in neonatal rat VSM cells, indicating a redifferentiation process. RNase protection assays defined thrombin as a se rum component that increases the abundance of SRI-MHC transcripts. Addition ally, serum and thrombin transiently elevated cytosolic Ca2+ concentrations , led to a biphasic extracellular signal-regulated kinase (ERK) phosphoryla tion, up-regulated a transfected SRI-MHC promoter construct, and induced ex pression of the contractile proteins SM-MHc and ol-actin, Pertussis toxin, N17-Ras/Raf, and PD98059 prevented both the serum- and thrombin-induced sec ond phase ERK phosphorylation and SM-MHc promoter activation. Constitutivel y active G alpha (q), G alphai, G alpha (12), and G alpha (13) failed to up -regulate SRI-MHC transcription, whereas G beta gamma concentration-depende ntly increased the SM-MHC promoter activity. Furthermore, the G beta gamma scavenger beta -adrenergic receptor kinase 1 C-terminal peptide abolished t he serum-mediated differentiation. We conclude that receptor-mediated diffe rentiation of VSM cells requires G beta gamma and an intact Ras/Raf/MEK/ERK signaling.