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Antagonism of Human Adiponectin Receptors and Their Membrane Progesterone Receptor Paralogs by TNFα and a Ceramidase Inhibitor

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journal contribution
posted on 23.06.2009, 00:00 by Brian R. Kupchak, Ibon Garitaonandia, Nancy Y. Villa, Jessica L. Smith, Thomas J. Lyons
The progestin and AdipoQ receptor (PAQR) family of proteins comprises three distinct structural classes, each with seemingly different agonist specificities. For example, Class I receptors, like the human adiponectin receptors (AdipoR1 and AdipoR2), sense proteins with a particular three-dimensional fold, while Class II receptors are nonclassical membrane receptors for the steroid hormone progesterone. Using a previously developed heterologous expression system to study PAQR receptor activity, we demonstrate that human PAQRs from all three classes are antagonized by both 1(S),2(R)-d-erythro-2-(N-myristoylamino)-1-phenyl-1-propanol, a ceramidase inhibitor, and TNFα, a homologue of adiponectin that functions antagonistically to both adiponectin and progesterone in human cells.