Endothelial nitric-oxide synthase reveals a new face in G protein signaling.
In this issue of Molecular Pharmacology, Andreeva et al. (p. 975) report a novel functional link between the heterotrimeric G protein G alpha12 and endothelial nitric-oxide synthase (eNOS). Based on studies characterizing the interaction of G alpha12 and the molecular chaperone Hsp90 and the interaction of eNOS and Hsp90, the group proposed an interaction between G alpha12 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 alpha12 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 alpha12-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.
Bilodeau
Matthew L
ML
Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232-6600, USA.
Hamm
Heidi E
HE
D000818:Animals; D004730:Endothelium, Vascular / Q000378:metabolism; D004795:Enzyme Stability; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000235:genetics / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism*; D020871:RNA Stability; D015398:Signal Transduction; D014162:Transfection
D018841:HSP90 Heat-Shock Proteins; D052250:Nitric Oxide Synthase Type III; D044365:GTP-Binding Protein alpha Subunits, G12-G13