Biochem Biophys Res Commun 2003,
PMID: 12763029
Kintscher, Ulrich; Bruemmer, Dennis; Blaschke, Florian; Unger, Thomas; Law, Ronald E
Many of the signaling events in VSMC stimulated by angiotensin II (AngII) are mediated by members of the mitogen-activated protein kinase (MAPK) family, including p38 MAPK. The role of p38 MAPK in AngII-mediated cell cycle regulation is poorly understood. Therefore, we examined the involvement of p38 MAPK signaling in AngII-stimulated DNA synthesis, phosphorylation of the retinoblastoma protein (Rb), and expression of the G1-phase cyclin D1 in human coronary artery smooth muscle cells (CASMC). AngII (1 microM) stimulated p38 MAPK and ERK1/2 activation. Pretreatment with the p38 MAPK inhibitors SB203580 (10 microM) (SB) or SKF-86002 (10 microM) (SKF) potently inhibited AngII-induced p38 MAPK activation, but enhanced AngII-mediated ERK1/2 activation. AngII-induced-phosphorylation of Rb (Ser 795 and Ser 807/811), -cyclin D1 expression, and -DNA synthesis was also markedly enhanced by pharmacological inhibition of the p38 MAPK pathway. The present study demonstrates that p38 MAPK negatively regulates AngII-induced ERK1/2 activity, Rb phosphorylation, cyclin D1 expression, and DNA-synthesis in human CASMC. These findings support an important role for p38 MAPK in modulating AngII-mediated VSMC hyperplasia.
Diseases/Pathways annotated by Medline MESH: MAP Kinase Signaling System
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Text Mining Data
cyclin D1 — p38: "
Therefore, we examined the
involvement of
p38 MAPK signaling in AngII stimulated DNA synthesis, phosphorylation of the retinoblastoma protein ( Rb ), and expression of the G1-phase
cyclin D1 in human coronary artery smooth muscle cells ( CASMC )
"
cyclin D1 — MAPK: "
Therefore, we examined the involvement of p38 MAPK signaling in AngII stimulated DNA synthesis, phosphorylation of the retinoblastoma protein ( Rb ), and expression of the G1-phase cyclin D1 in human coronary artery smooth muscle cells ( CASMC )
"
cyclin D1 → MAPK: "
The present study demonstrates that p38 MAPK negatively regulates AngII induced ERK1/2 activity, Rb phosphorylation, cyclin D1 expression, and DNA-synthesis in human CASMC
"
ERK1/2 → MAPK: "
The present study demonstrates that p38 MAPK negatively regulates AngII induced ERK1/2 activity, Rb phosphorylation, cyclin D1 expression, and DNA-synthesis in human CASMC
"
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