Endothelial Nitric-Oxide Synthase Reveals a New Face in G Protein Signaling: Fig. 1.

Abstract

In this issue of Molecular Pharmacology, Andreeva et al. (p. 975) report a novel functional link between the heterotrimeric G protein G␣ 12 and endothelial nitric-oxide synthase (eNOS). 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 cotransfection of G␣ 12 and eNOS expression vectors increased 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.

Regulation of apoptosis signal‐regulating kinase 1 degradation by Gα13

“…Together with our previous study (34) (also see a comment in ref. 43), the findings reported here also outline a new paradigm in G protein-coupled signaling. We have shown previously that G␣12 can increase expression levels of eNOS by stabilizing both mRNA and protein (34).…”