Author/Editor		Deželak, Matjaž; Bavec, Aljoša
Title		Third intracellular loop of glucagon like-peptide-1 receptor is coupled with endogenous mono-ADP-ribosyltransferase - Novel type of receptor regulation?
Type		članek
Source		Eur J Pharmacol
Vol. and No.		Letnik 666
Publication year		2011
Volume		str. 35-42
Language		eng
Abstract		Our previous studies revealed the main role of the third intracellular loop (IC(3)) of glucagon-like peptide-1 receptor (GLP-1 receptor), in G-protein activation, where the presence or absence of agonist and the receptor phosphorylation seemed to be the only regulatory mechanisms. In order to further study the signaling mechanisms of GLP-1 receptor, we investigated the effect of the third intracellular loop-derived peptide on endogenous mono-ADP-ribosyltransferase mediated mono-ADP-ribosylation of G-proteins beta subunit in CHO cells. Results showed an inhibitory effect of IC(3) peptide on mono-ADP-ribosylation of beta subunit, obviously via the mechanism of competitive inhibition. Excluding the activity of this inhibitory mechanism via pertussis toxin-sensitive G proteins, the direct functional coupling of IC(3) of GLP-1 receptor and endogenous mono-ADP-ribosyltransferase was confirmed. We suggest that this arginine specific enzymatic posttranslational modification of third intracellular loop of GLP-1 receptor might represent a possible novel mechanism of receptor activity regulation and the pharmacological potential in treatment of diabetes mellitus type 2.
Descriptors		RECEPTORS, GLUCAGON RECEPTORS, PEPTIDE GTP-BINDING PROTEINS PHOSPHORYLATION NAD+ ADP-RIBOSYLTRANSFERASE PROTEIN PROCESSING, POST-TRANSLATIONAL ARGININE CHO CELLS CIRCULAR DICHROISM