Regulation of insulin-like growth factor-binding protein-5 expression during Schwann cell differentiation.
We have reported that immortalized Schwann cells (SC) express the insulin-like growth factor I receptor and IGF-binding protein-5 (IGFBP-5). IGF-I promotes SC survival and protects IGFBP-5 in SC-conditioned medium from proteolysis. In the current study we examined the roles of IGF-I and IGFBP-5 in primary SC. IGF-I enhances primary SC differentiation and gene and protein expression of IGFBP-5 and the myelinating protein, P0. SC that stably overexpress human IGFBP-5 also have higher levels of P0 gene expression. The phosphatidylinositol-3 kinase inhibitor (LY294002), but not the mitogen-activated protein kinase kinase inhibitor (PD98059), blocks IGF-I enhancement of IGFBP-5 gene and protein expression. Collectively, these results suggest that IGF-I promotes SC differentiation, and this may occur in part by enhancing IGFBP-5 expression via phosphatidylinositol-3 kinase activation. These data support a link between enhanced IGFBP-5 expression and cellular differentiation.
Cheng
H L
HL
Department of Neurology, University of Michigan, Ann Arbor 48109-0588, USA.
Shy
M
M
Feldman
E L
EL
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D006801:Humans; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D018993:Myelin P0 Protein / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000166:cytology* / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D018975:Insulin-Like Growth Factor Binding Protein 5; D018993:Myelin P0 Protein; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases