Differential regulation of p27(kip1) levels and CDK activities by hypertrophic and hyperplastic agents in vascular smooth muscle cells

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Abstract

To understand the molecular mechanisms that determine the fate of a cell to undergo either hypertrophy or hyperplasia, we studied the effects of angiotensin II (Ang II) and platelet-derived growth factor (PDGF)-BB, hypertrophic and hyperplastic agents, respectively, on the modulation of G1/S transition molecules in smooth muscle cells. Ang II increased protein synthesis while PDGF-BB induced both DNA and protein synthesis. Ang II had no significant effect on the steady-state levels of cyclin-dependent kinase (CDK) inhibitor (CDKI), p27(kip1), and on the activities of CDK2 and CDK4, although it caused a modest increase in cyclin E levels. In contrast, PDGF-BB induced depletion of p27(kip1) and increased cyclins D1 and E levels and CDK2 and CDK4 activities. Reflecting its lack of effect on CDK activities, Ang II failed to phosphorylate tumor suppressor retinoblastoma protein, Rb. PDGF-BB, on the other hand, induced phosphorylation of Rb, consistent with its ability to activate CDKs. Together, these findings suggest that Ang II-induced hypertrophy may be due to its failure to activate cellular signaling events required for G1/S transition. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)525-532
Number of pages8
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1448
Issue number3
DOIs
StatePublished - Jan 11 1999

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Cyclin-Dependent Kinases
Vascular Smooth Muscle
Angiotensin II
Smooth Muscle Myocytes
Cyclin E
Hypertrophy
Cyclin-Dependent Kinase Inhibitor p27
Tumor Suppressor Proteins
Retinoblastoma Protein
Cyclin D1
Hyperplasia
Proteins
Phosphorylation
platelet-derived growth factor BB
DNA

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

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title = "Differential regulation of p27(kip1) levels and CDK activities by hypertrophic and hyperplastic agents in vascular smooth muscle cells",
abstract = "To understand the molecular mechanisms that determine the fate of a cell to undergo either hypertrophy or hyperplasia, we studied the effects of angiotensin II (Ang II) and platelet-derived growth factor (PDGF)-BB, hypertrophic and hyperplastic agents, respectively, on the modulation of G1/S transition molecules in smooth muscle cells. Ang II increased protein synthesis while PDGF-BB induced both DNA and protein synthesis. Ang II had no significant effect on the steady-state levels of cyclin-dependent kinase (CDK) inhibitor (CDKI), p27(kip1), and on the activities of CDK2 and CDK4, although it caused a modest increase in cyclin E levels. In contrast, PDGF-BB induced depletion of p27(kip1) and increased cyclins D1 and E levels and CDK2 and CDK4 activities. Reflecting its lack of effect on CDK activities, Ang II failed to phosphorylate tumor suppressor retinoblastoma protein, Rb. PDGF-BB, on the other hand, induced phosphorylation of Rb, consistent with its ability to activate CDKs. Together, these findings suggest that Ang II-induced hypertrophy may be due to its failure to activate cellular signaling events required for G1/S transition. Copyright (C) 1999 Elsevier Science B.V.",
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