Simon_2006_J.Biol.Chem_281_40310

Reference

Title : The proto-oncogene SET interacts with muscarinic receptors and attenuates receptor signaling - Simon_2006_J.Biol.Chem_281_40310
Author(s) : Simon V , Guidry J , Gettys TW , Tobin AB , Lanier SM
Ref : Journal of Biological Chemistry , 281 :40310 , 2006
Abstract :

G protein-coupled receptors mediate cell responses to extracellular stimuli and likely function in the context of a larger signal transduction complex. Utilizing the third intracellular loop of a G protein-coupled receptor in glutathione S-transferase pulldown assays from rat brain lysates coupled with high sensitivity detection methods and subsequent functional studies, we report the identification of SET as a regulator of muscarinic receptor signaling. SET is a putative oncogene reported to inhibit protein phosphatase 2A and regulate gene transcription. SET binds the carboxyl region of the M3-muscarinic receptor i3 loop, and endogenous SET co-immunoprecipitates with intact M3 muscarinic receptor expressed in cells. Small interfering RNA knockdown of endogenous SET in Chinese hamster ovary cells stably expressing the M3 muscarinic receptor augmented receptor-mediated mobilization of intracellular calcium by approximately 35% with no change in agonist EC(50), indicating that interaction of SET with the M3 muscarinic receptor reduces its signaling capacity. SET knockdown had no effect on the mobilization of intracellular calcium by the P2-purinergic receptor, ionomycin, or a direct activator of phospholipase C, indicating a specific regulation of M3 muscarinic receptor signaling. These data provide expanded functionality for SET and a previously unrecognized mechanism for regulation of GPCR signaling capacity.

PubMedSearch : Simon_2006_J.Biol.Chem_281_40310
PubMedID: 17065150

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Citations formats

Simon V, Guidry J, Gettys TW, Tobin AB, Lanier SM (2006)
The proto-oncogene SET interacts with muscarinic receptors and attenuates receptor signaling
Journal of Biological Chemistry 281 :40310

Simon V, Guidry J, Gettys TW, Tobin AB, Lanier SM (2006)
Journal of Biological Chemistry 281 :40310