RT Journal Article
SR Electronic
T1 Influence of the Membrane Lipid Structure on Signal Processing via G Protein-Coupled Receptors
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 210
OP 217
DO 10.1124/mol.105.011692
VO 68
IS 1
A1 Yang, Qing
A1 Alemany, Regina
A1 Casas, Jesús
A1 Kitajka, Klára
A1 Lanier, Stephen M.
A1 Escribá, Pablo V.
YR 2005
UL http://molpharm.aspetjournals.org/content/68/1/210.abstract
AB We have recently reported that lipid structure regulates the interaction with membranes, recruitment to membranes, and distribution to membrane domains of heterotrimeric Gαβγ proteins, Gα subunits, and Gβγ dimers (J Biol Chem 279:36540–36545, 2004). Here, we demonstrate that modulation of the membrane structure not only determines G protein localization but also regulates the function of G proteins and related signaling proteins. In this context, the antitumor drug daunorubicin (daunomycin) and oleic acid changed the membrane structure and inhibited G protein activity in biological membranes. They also induced marked changes in the activity of the α2A/D-adrenergic receptor and adenylyl cyclase. In contrast, elaidic and stearic acid did not change the activity of the above-mentioned proteins. These fatty acids are chemical but not structural analogs of oleic acid, supporting the structural basis of the modulation of membrane lipid organization and subsequent regulation of G protein-coupled receptor signaling. In addition, oleic acid (and also daunorubicin) did not alter G protein activity in a membrane-free system, further demonstrating the involvement of membrane structure in this signal modulation. The present work also unravels in part the molecular bases involved in the antihypertensive (Hypertension 43:249–254, 2004) and anticancer (Mol Pharmacol 67:531–540, 2005) activities of synthetic oleic acid derivatives (e.g., 2-hydroxyoleic acid) as well as the molecular bases of the effects of diet fats on human health.