Protein kinase A-dependent phosphorylation of GLUT2 in pancreatic beta cells.

Details

Serval ID
serval:BIB_52E1BFFA9EC8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Protein kinase A-dependent phosphorylation of GLUT2 in pancreatic beta cells.
Journal
Journal of Biological Chemistry
Author(s)
Thorens B., Dériaz N., Bosco D., DeVos A., Pipeleers D., Schuit F., Meda P., Porret A.
ISSN
0021-9258[print], 0021-9258[linking]
Publication state
Published
Issued date
1996
Volume
271
Number
14
Pages
8075-8081
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Abstract
In pancreatic beta cells, cyclic AMP-dependent protein kinase regulates many cellular processes including the potentiation of insulin secretion. The substrates for this kinase, however, have not been biochemically characterized. Here we demonstrate that the glucose transporter GLUT2 is rapidly phosphorylated by protein kinase A following activation of adenylyl cyclase by forskolin or the incretin hormone glucagon-like peptide-1. We show that serines 489 and 501/503 and threonine 510 in the carboxyl-terminal tail of the transporter are the in vitro and in vivo sites of phosphorylation. Stimulation of GLUT2 phosphorylation in beta cells reduces the initial rate of 3-O-methyl glucose uptake by approximately 48% but does not change the Michaelis constant. Similar differences in transport kinetics are observed when comparing the transport activity of GLUT2 mutants stably expressed in insulinoma cell lines and containing glutamates or alanines at the phosphorylation sites. These data indicate that phosphorylation of GLUT2 carboxyl-terminal tail modifies the rate of transport. This lends further support for an important role of the transporter cytoplasmic tail in the modulation of catalytic activity. Finally, because activation of protein kinase A stimulates glucose-induced insulin secretion, we discuss the possible involvement of GLUT2 phosphorylation in the amplification of the glucose signaling process.
Keywords
3-O-Methylglucose, Amino Acid Sequence, Animals, Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors, Cyclic AMP-Dependent Protein Kinases/metabolism, Enzyme Inhibitors/pharmacology, Forskolin/pharmacology, Glucagon-Like Peptide 1, Glucose Transporter Type 2, Isoquinolines/pharmacology, Kinetics, Methylglucosides/metabolism, Molecular Sequence Data, Monosaccharide Transport Proteins/metabolism, Peptides/pharmacology, Phosphorylation, Rats, Sulfonamides, Tumor Cells, Cultured
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 13:41
Last modification date
20/08/2019 14:08
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