b-catenin mediates insulin-like growth factor-I actions to promote cyclin D1 mRNA expression, cell proliferation and survival in oligodendroglial cultures
By promoting cell proliferation, survival and maturation insulin-like growth factor (IGF)-I is essential to the normal growth and development of the central nervous system. It is clear that IGF-I actions are primarily mediated by the type I IGF receptor (IGF1R), and that phosphoinositide 3 (PI3)-Akt...
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Published in | Glia Vol. 58; no. 9; pp. 1031 - 1041 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
01.07.2010
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Online Access | Get full text |
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Summary: | By promoting cell proliferation, survival and maturation insulin-like growth factor (IGF)-I is essential to the normal growth and development of the central nervous system. It is clear that IGF-I actions are primarily mediated by the type I IGF receptor (IGF1R), and that phosphoinositide 3 (PI3)-Akt kinases and MAP kinases signal many of IGF-I-IGF1R actions in neural cells, including oligodendrocyte lineage cells. The precise downstream targets of these signaling pathways, however, remain to be defined. We studied oligodendroglial cells to determine whether -catenin, a molecule that is a downstream target of glycogen synthase kinase-3 (GSK3) and plays a key role in the Wnt canonical signaling pathway, mediates IGF-I actions. We found that IGF-I increases -catenin protein abundance within an hour after IGF-I-induced phosphorylation of Akt and GSK3. Inhibiting the PI3-Akt pathway suppressed IGF-I-induced increases in -catenin and cyclin D1 mRNA, while suppression of GSK3 activity simulated IGF-I actions. Knocking-down -catenin mRNA by RNA interference suppressed IGF-I-stimulated increases in the abundance of cyclin D1 mRNA, cell proliferation, and cell survival. Our data suggest that -catenin is an important downstream molecule in the PI3-Akt-GSK3 pathway, and as such it mediates IGF-I upregulation of cyclin D1 mRNA and promotion of cell proliferation and survival in oligodendroglial cells. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 content type line 23 ObjectType-Feature-2 |
ISSN: | 0894-1491 |
DOI: | 10.1002/glia.20984 |