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Received for publication December 23, 2005.
Revised December 22, 2005.
Accepted for publication December 23, 2005.
In this issue of Molecular Pharmacology Andreeva et al. report a novel functional link between the heterotrimeric G protein G
12 and endothelial nitric oxide synthase (eNOS) (Andreeva et al., 2006). Based on studies characterizing the interaction of G
12 and the molecular chaperone Hsp90 and the interaction of eNOS and Hsp90, the group proposed an interaction between G
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
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
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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