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Title: Differential G-protein-coupled receptor phosphorylation provides evidence for a signaling bar code.
Authors: Butcher, AJ
Prihandoko, R
Kong, KC
McWilliams, P
Edwards, JM
Bottrill, A
Mistry, S
Tobin, AB
First Published: 1-Apr-2011
Citation: J BIOL CHEM, 2011, 286 (13), pp. 11506-11518
Abstract: G-protein-coupled receptors are hyper-phosphorylated in a process that controls receptor coupling to downstream signaling pathways. The pattern of receptor phosphorylation has been proposed to generate a "bar code" that can be varied in a tissue-specific manner to direct physiologically relevant receptor signaling. If such a mechanism existed, receptors would be expected to be phosphorylated in a cell/tissue-specific manner. Using tryptic phosphopeptide maps, mass spectrometry, and phospho-specific antibodies, it was determined here that the prototypical G(q/11)-coupled M(3)-muscarinic receptor was indeed differentially phosphorylated in various cell and tissue types supporting a role for differential receptor phosphorylation in directing tissue-specific signaling. Furthermore, the phosphorylation profile of the M(3)-muscarinic receptor was also dependent on the stimulus. Full and partial agonists to the M(3)-muscarinic receptor were observed to direct phosphorylation preferentially to specific sites. This hitherto unappreciated property of ligands raises the possibility that one mechanism underlying ligand bias/functional selectivity, a process where ligands direct receptors to preferred signaling pathways, may be centered on the capacity of ligands to promote receptor phosphorylation at specific sites.
DOI Link: 10.1074/jbc.M110.154526
eISSN: 1083-351X
Type: Journal Article
Appears in Collections:Published Articles, Dept. of Cell Physiology and Pharmacology

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