Author/Editor		Bavec, Aljoša; Haellbrink, Mattias; Langel, Uelo; Zorko, Matjaž
Title		Different role of intracellular loops of glucagon-like peptide-1 receptor in G-protein coupling
Type		članek
Source		Regul Pept
Vol. and No.		Letnik 111, št. 1-3
Publication year		2003
Volume		str. 137-44
Language		eng
Abstract		Previous studies revealed the importance of the third intracellular loop of glucagon-like peptide-1 receptor (GLP-1R) in coupling to G(s) and G(i1) proteins. In order to further study the signaling mechanisms of GLP-1R, we tested three peptides, corresponding to the sequences of the first (IC(1)), the second (IC(2)), and the third (IC(3)) intracellular loop of GLP-1R, for their interactions with heterotrimeric G-proteins of different types (G(alphas), G(alphao), G(alphai1), and G(alpha11) plus G(beta1gamma2)) overexpressed in sf9 cells. IC(3) peptide powerfully stimulates all types of tested G-proteins, whereas IC(1) and IC(2) peptides show differential effects on G-proteins. Both IC(1) and IC(2) peptides activate G(s) and cooperate with IC(3) peptide in its stimulation. G(o) is not affected by IC(1) and IC(2). G(i1) and G(11) are not affected by IC(1), but are activated by IC(2), which in activation cooperates with IC(3). We suggest that GLP-1R is not coupled only to G(s) and G(i1), as shown previously, but also to G(o) and G(11). IC(3) loop is the main switch that mediates signaling via GLP-1R to G-proteins, while IC(1) and IC(2) loops are important in discrimination between different types of G-proteins.
Descriptors		GTP-BINDING PROTEINS SIGNAL TRANSDUCTION ADENOSINE DIPHOSPHATE RIBOSE PERTUSSIS TOXINS CIRCULAR DICHROISM CELLS, CULTURED CHOLERA TOXIN