A dileucine motif in the C terminus of the b2-adrenergic receptor is involved in receptor internalization (adenylyl cyclaseyreceptor sequestrationyChinese hamster ovary cells)

1997 
The cytoplasmic C terminus of the b2- adrenergic receptor and many other G protein-coupled recep- tors contains a dileucine sequence that has been implicated in endosomeylysosome targeting of diverse proteins. In the present study, we provide evidence for an essential role of this motif in the agonist-induced internalization of the b2- adrenergic receptor. Mutation of Leu-339 andyor Leu-340 to Ala caused little changes in surface expression, ligand bind- ing, G protein coupling, and signaling to adenylyl cyclase, when these receptors were transiently or stably expressed in CHO or HEK-293 cells. However, agonist-induced receptor internalization was markedly impaired in the L 339,340 A double mutant and reduced in the two single mutants. This impair- ment in receptor internalization was seen by using various approaches to determine internalization: binding of hydro- phobic vs. hydrophilic ligands, loss of surface b2-adrenergic receptor immunoreactivity, and immunof luorescence micros- copy. The selective effects of these mutations suggest that the C-terminal dileucine motif is involved in agonist-induced internalization of the b2-adrenergic receptor.
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