An SH2 domain-containing 5' inositolphosphatase inhibits insulin-induced GLUT4 translocation and growth factor-induced actin filament rearrangement.

Details

Serval ID
serval:BIB_C9A03F491A5A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
An SH2 domain-containing 5' inositolphosphatase inhibits insulin-induced GLUT4 translocation and growth factor-induced actin filament rearrangement.
Journal
Molecular and cellular biology
Author(s)
Vollenweider P., Clodi M., Martin S.S., Imamura T., Kavanaugh W.M., Olefsky J.M.
ISSN
0270-7306
Publication state
Published
Issued date
1999
Peer-reviewed
Oui
Volume
19
Number
2
Pages
1081-91
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, U.S. Gov't, P.H.S. - Publication Status: ppublish
Abstract
Tyrosine kinase receptors lead to rapid activation of phosphatidylinositol 3-kinase (PI3 kinase) and the subsequent formation of phosphatidylinositides (PtdIns) 3,4-P2 and PtdIns 3,4, 5-P3, which are thought to be involved in signaling for glucose transporter GLUT4 translocation, cytoskeletal rearrangement, and DNA synthesis. However, the specific role of each of these PtdIns in insulin and growth factor signaling is still mainly unknown. Therefore, we assessed, in the current study, the effect of SH2-containing inositol phosphatase (SHIP) expression on these biological effects. SHIP is a 5' phosphatase that decreases the intracellular levels of PtdIns 3,4,5-P3. Expression of SHIP after nuclear microinjection in 3T3-L1 adipocytes inhibited insulin-induced GLUT4 translocation by 100 +/- 21% (mean +/- the standard error) at submaximal (3 ng/ml) and 64 +/- 5% at maximal (10 ng/ml) insulin concentrations (P < 0.05 and P < 0.001, respectively). A catalytically inactive mutant of SHIP had no effect on insulin-induced GLUT4 translocation. Furthermore, SHIP also abolished GLUT4 translocation induced by a membrane-targeted catalytic subunit of PI3 kinase. In addition, insulin-, insulin-like growth factor I (IGF-I)-, and platelet-derived growth factor-induced cytoskeletal rearrangement, i.e., membrane ruffling, was significantly inhibited (78 +/- 10, 64 +/- 3, and 62 +/- 5%, respectively; P < 0.05 for all) in 3T3-L1 adipocytes. In a rat fibroblast cell line overexpressing the human insulin receptor (HIRc-B), SHIP inhibited membrane ruffling induced by insulin and IGF-I by 76 +/- 3% (P < 0.001) and 68 +/- 5% (P < 0.005), respectively. However, growth factor-induced stress fiber breakdown was not affected by SHIP expression. Finally, SHIP decreased significantly growth factor-induced mitogen-activated protein kinase activation and DNA synthesis. Expression of the catalytically inactive mutant had no effect on these cellular responses. In summary, our results show that expression of SHIP inhibits insulin-induced GLUT4 translocation, growth factor-induced membrane ruffling, and DNA synthesis, indicating that PtdIns 3,4,5-P3 is the key phospholipid product mediating these biological actions.
Keywords
1-Phosphatidylinositol 3-Kinase, 3T3 Cells, Actins, Amino Acid Sequence, Animals, Biological Transport, Active, Bromodeoxyuridine, Calcium-Calmodulin-Dependent Protein Kinases, Cell Line, Cell Membrane, DNA, Enzyme Activation, Glucose Transporter Type 4, Guanosine 5'-O-(3-Thiotriphosphate), Humans, Insulin, Insulin-Like Growth Factor I, Mice, Monosaccharide Transport Proteins, Muscle Proteins, Mutation, Phosphatidylinositol Phosphates, Phosphoric Monoester Hydrolases, Platelet-Derived Growth Factor, Rats, Recombinant Proteins, Sequence Deletion, Transfection, src Homology Domains
Pubmed
Web of science
Create date
25/01/2008 14:06
Last modification date
20/08/2019 15:44
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