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Title: Differential regulation of p27kip1 levels and CDK activities by hypertrophic and hyperplastic agents in vascular smooth muscle cells. Author: Rao GN. Journal: Biochim Biophys Acta; 1999 Jan 11; 1448(3):525-32. PubMed ID: 9990305. 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), p27kip1, 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 p27kip1 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.[Abstract] [Full Text] [Related] [New Search]