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Molecular Pharmacology Fast Forward
First published on December 23, 2005; DOI: 10.1124/mol.105.022038


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Received for publication December 23, 2005.
Revised December 22, 2005.
Accepted for publication December 23, 2005.

eNOS reveals a new face in G protein signaling (Relates to Article by Andreeva, et al. FastForward 2 December 2005)

Matthew L Bilodeau 1 Heidi E. Hamm 1*

1 Vanderbilt University

* Address correspondence to: E-mail: heidi.hamm{at}vanderbilt.edu

Abstract

In this issue of Molecular Pharmacology Andreeva et al. report a novel functional link between the heterotrimeric G protein G{alpha}12 and endothelial nitric oxide synthase (eNOS) (Andreeva et al., 2006). Based on studies characterizing the interaction of G{alpha}12 and the molecular chaperone Hsp90 and the interaction of eNOS and Hsp90, the group proposed an interaction between G{alpha}12 and eNOS and sought to determine the regulatory mechanisms including the inferred dependence on Hsp90. Their experiments using an overexpression model lead to the observation that the co-transfection of G{alpha}12 and eNOS expression vectors increased the overall eNOS expression. Additional studies in the overexpression model and in human umbilical vein endothelial cells (HUVEC) provide evidence for a mechanism that involves G{alpha}12-dependent stabilization of eNOS protein and possibly mRNA. These data present yet another paradigm by which heterotrimeric G proteins, through stabilization of target proteins, can regulate the activity of downstream signaling pathways.


Key words: Thrombin/PAR, Nitric oxide, Nitric oxide synthases, Gi family, Gs family, Gq/11 family, G12,13;other G's, G protein regulation


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M. A. Kutuzov, A. V. Andreeva, and T. A. Voyno-Yasenetskaya
Regulation of apoptosis signal-regulating kinase 1 degradation by G{alpha}13
FASEB J, November 1, 2007; 21(13): 3727 - 3736.
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