PT  - JOURNAL ARTICLE
AU  - Liang, Mei
AU  - Eason, Margaret G.
AU  - Jewell-Motz, Elizabeth A.
AU  - Williams, Mark A.
AU  - Theiss, Cheryl T.
AU  - Dorn, Gerald W.
AU  - Liggett, Stephen B.
TI  - Phosphorylation and Functional Desensitization of the  α<sub>2A</sub>-Adrenergic Receptor by Protein Kinase C
AID  - 10.1124/mol.54.1.44
DP  - 1998 Jul 01
TA  - Molecular Pharmacology
PG  - 44--49
VI  - 54
IP  - 1
4099  - http://molpharm.aspetjournals.org/content/54/1/44.short
4100  - http://molpharm.aspetjournals.org/content/54/1/44.full
SO  - Mol Pharmacol1998 Jul 01; 54
AB  - We have investigated the potential for protein kinase C (PKC) to phosphorylate and desensitize the α2A-adrenergic receptor (α2AAR). In whole-cell phosphorylation studies, recombinantly expressed human α2AAR displayed an increase in phosphorylation after short-term exposure to 100 nmphorbol 12-myristate-13-acetate (PMA) that was blocked by preincubation with a PKC inhibitor. This increase in receptor phosphorylation over basal amounted to 172 ± 40% in COS-7 cells and 201 ± 40% in Chinese hamster ovary cells. In permanently transfected Chinese hamster fibroblast cells, PKC activation by brief exposure of the cells to PMA resulted in a marked desensitization of α2AAR function, amounting to a 68 ± 4% decrease in the maximal agonist (UK14304)-stimulated intracellular calcium release. Such desensitization was blocked by the PKC inhibitor bisindolylmaleimide I and was not evoked by an inactive phorbol ester. The desensitization of this agonist response was not caused by PKC-mediated augmentation of G protein-coupled receptor kinase activity, because PMA-promoted desensitization of a mutated α2AAR that lacked G protein-coupled receptor kinase phosphorylation sites was identical to that of wild-type α2AAR. To test whether PKC phosphorylation is a mechanism by which α2AAR can be regulated by other receptors, the α1bAR was co-expressed with the α2AAR in Chinese hamster ovary cells. Upon selective activation of α1bAR, the function of α2AAR underwent a 53 ± 5% desensitization. Thus, cellular events that result in PKC activation promote phosphorylation of the α2AAR and lead to substantial desensitization of receptor function. This heterologous regulation also represents a mechanism by which rapid crosstalk between the α2AAR and other receptors can occur.