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Sci. STKE, 3 December 2002
Vol. 2002, Issue 161, p. tw453
[DOI: 10.1126/stke.2002.161.tw453]

EDITORS' CHOICE

Nitric Oxide Rho's Double Knockdown of eNOS

Endothelial nitric oxide synthase (eNOS) produces nitric oxide (NO) to regulate vascular tone and integrity. eNOS is controlled at both transcriptional and translational levels. For example, the small guanosine triphosphatase (GTPase) Rho and its downstream effector Rho kinase (ROCK) regulate eNOS gene expression by affecting its mRNA stability. In addition, phosphorylation by protein kinase B (PKB, also called Akt) increases eNOS enzymatic activity. Ming et al. have discovered cross-talk between these two modes of regulation. Ectopic expression of constitutively active RhoA or ROCK in endothelial cells not only decreased eNOS expression but also inhibited eNOS phosphorylation by PKB. Treatment of endothelial cells with the pathological stimulus thrombin, which activates the Rho pathway, also decreased both PKB and eNOS activities and eNOS expression. When the Rho signaling pathway was blocked in endothelial cells, expression of activated PKB restored eNOS activity, but not eNOS expression, which indicates that PKB only links Rho to enzyme activity but not expression. The double effect of Rho may be needed to achieve rapid and long-term decrease in NO production.

X. F. Ming, H. Viswambharan, C. Barandier, J. Ruffieux, K. Kaibuchi, S. Rusconi, Z. Yang, Rho GTPase/Rho kinase negatively regulates endothelial nitric oxide synthase phosphorylation through the inhibition of protein kinase B/Akt in human endothelial cells. Mol. Cell. Biol. 22, 8467-8477 (2002). [Abstract] [Full Text]

Citation: Rho's Double Knockdown of eNOS. Sci. STKE 2002, tw453 (2002).



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