PT  - JOURNAL ARTICLE
AU  - R B Clark
AU  - J Friedman
AU  - R A Dixon
AU  - C D Strader
TI  - Identification of a specific site required for rapid heterologous desensitization of the beta-adrenergic receptor by cAMP-dependent protein kinase.
DP  - 1989 Sep 01
TA  - Molecular Pharmacology
PG  - 343--348
VI  - 36
IP  - 3
4099  - http://molpharm.aspetjournals.org/content/36/3/343.short
4100  - http://molpharm.aspetjournals.org/content/36/3/343.full
SO  - Mol Pharmacol1989 Sep 01; 36
AB  - The molecular basis for heterologous desensitization of the beta-adrenergic receptor (beta AR) was investigated by site-directed mutagenesis of the beta AR protein. Rapid heterologous desensitization of agonist-stimulated adenylyl cyclase activity was observed when L cells expressing the wild-type beta AR were incubated with 50 nM epinephrine. This desensitization response could be mimicked in a cell-free system by incubation with cAMP-dependent protein kinase (cA.PK). Deletion of amino acid residues 259-262 from the beta AR, removing one of the two consensus sequences in the receptor for phosphorylation by cA.PK, abolished the ability of the receptor to undergo rapid heterologous desensitization. In contrast, deletion of the other cA.PK consensus sequence (residues 343-348) or truncation of the Ser/Thr-rich C-terminal tail of the beta AR (deletion of residues 354-418) did not affect this heterologous desensitization process. These results suggest that the action of cA.PK on amino acid residue(s) contained within the sequence 259-262 of the beta AR is required for rapid heterologous desensitization of the receptor in response to agonists.