Author/Editor		Bavec, Aljoša
Title		Vloga znotrajceličnih zank receptorja za glukagonu podobni peptid-1 pri prenosu signala
Translated title		Different role of intracellular loops of glucagon-like peptide-1 receptor in signal transduction
Type		monografija
Place		Ljubljana
Publisher		Medicinska fakulteta
Publication year		2003
Volume		str. 100
Language		slo
Abstract		Previous studies revealed the importance of the third intracellular loop of glucagon-like peptide-1 receptor (GLP-1R) in coupling to Gs and Gi1 proteins. In order to further study the signaling mechanisms of GLP-1R, we tested three peptides, corresponding to the sequences of the first (IC1), the second (IC2), and the third (IC3) intracellular loop of GLP-1R, for their interactions with heterotrimeric G-proteins of different types (Gas, Ga0, and Ga11 plus B1y2) overexpressed in sf9 cells. IC3 peptide powerfullystimulates all types of tested G-proteins whereas IC1 and IC2 peptides show differential effects on G proteins. Both, IC2 peptides activate Gs and cooperate with IC3 peptide in its stimulation. G0 is not affected by IC1 and IC2. Gi1 and G11 are not affected bz IC1 but are activated bz IC2, which in activation cooperates with IC3. We suggest that GLP-1R is not coupled only to Gs and Gil, but also to G0 and G11. IC3 loop is the main switch that mediates signaling via GLP-1R to G-proteins, while IC1and IC2 loops are important in discrimination between different types of G-proteins. Structural changes of IC3 peptide in its effect on G-proteins. IC3 peptide adopts much less B-structure at lower than at higher micromolar concentration. It would be possible that at higher concentrations the IC3 structure is changed from "switch off" to "switch on" conformation that stimulates Gs, G0, Gil and G11-proteins. Additionally, increase of the amount of B-structure might also reflect the aggregation of IC3 peptide at higher concentrations into a oligomeric structures such as dimers. Molecular model of GLP-1 dimer revealed the possible interaction of monomers in the region of IC3 loops. (Abstract truncated at 2000 characters).
Descriptors		GTP-BINDING PROTEINS AMINO ACID SEQUENCE SIGNAL TRANSDUCTION PERTUSSIS TOXINS CELLS, CULTURED ADENOSINE DIPHOSPHATE RIBOSE RECOMBINANT FUSION PROTEINS