Author
LI, XIAOJIE - CHINA AGRICULTURAL UNIV | |
LI, DEFA - CHINA AGRICULTURAL UNIV | |
WANG, Y - BAYLOR COLLEGE MED | |
QIAO, SHIYAN - CHINA AGRICULTURAL UNIV | |
CHANG, BENNY - BAYLOR COLLEGE MED | |
Burrin, Douglas - Doug | |
CHAN, LAWRENCE - BAYLOR COLLEGE MED | |
Guan, Xin Fu |
Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Abstract Only Publication Acceptance Date: 4/1/2007 Publication Date: 4/1/2007 Citation: Li, X., Li, D., Wang, Y., Qiao, S., Chang, B.H., Burrin, D.G., Chan, L., Guan, X. 2007. Glucagon-like peptide-2 activates the mTOR signaling through a PI3-kinase-Akt-dependent pathway [abstract]. Journal of Federation of American Societies for Experimental Biology. 21(6):A1075-A1076. Interpretive Summary: Technical Abstract: Glucagon-like peptide-2 (GLP-2) is nutrient-responsive neuropeptide that exerts diverse actions in the gastrointestinal tract. We have shown that GLP-2-stimulated mucosal growth occurred in vivo with an increased rate of protein synthesis in the neonatal intestine, which was associated with up-regulated phosphorylation of the Akt kinase. Evidence indicates that protein translation is controlled by the mammalian target of rapamycine (mTOR) signaling pathway. Thus, we hypothesized that GLP-2 receptor activation intracellularly stimulates the mTOR signaling through the phosphatidylinositol 3 (PI3)-kinase-Akt pathway. The HEK 293 cells were trasfected with a full-length cDNA of human GLP-2 receptor and treated with human GLP-2 with/without pre-treatment of a PI3-kinase inhibitor (LY294002). We found that GLP-2 dose-dependetly stimulated Akt phosphorylation at Ser473 and Thr308, which were suppressed by LY294002 at 60% and 30%, respectively. Moreover, GLP-2 stimulated mTOR phosphorylation at Ser2448, thus activating p70S6 kinase and inactivating the elF4E inhibitor (4E-BP1) by inducing phosphorylation of the p70S6 at Thr389 and the 4E-BP1 at Thr37/46, which were suppressed by LY294002 at 35% and 20%, respectively. We concluded that GLP-2-mediated activation of the mTOR signaling might be involved in GLP-2-stimulated mucosal protein synthesis, and was partially mediated by the PI3-kinase-Akt signaling pathway. |