title: Phosphatidylinositol-3 kinase p85 enhances expression from the myelin basic protein promoter in oligodendrocytes.
abstract: Phosphatidylinositol-3 kinase (PI3K) is a family of enzymes that phosphorylates the D3 position of phosphoinositides in membranes which can then act as a second messenger and affect many essential cellular processes such as survival, proliferation and differentiation. Class IA PI3K is composed of two subunits: a regulatory subunit, p85, and a catalytic subunit, p110. The p85 subunit is composed of several adapter domains which, upon interaction with the appropriate molecules, transmit the signal to activate p110. We have used the spontaneously immortalized oligodendrocyte cell line, CG4, to examine the role of PI3K in maturation of the oligodendrocyte. We show that overexpression of the p85 subunit enhances expression of myelin basic protein (MBP) upon differentiation of CG4 cells and primary oligodendrocytes. In experiments in CG4 cells, neither cotransfection with the tumor suppressor PTEN, which dephosphorylates the D3 position of phosphoinositides, nor inhibition of PI3K activity with wortmannin mimics this effect. Further, we have shown that this effect is dependent on the coexpression of the two SH2 domains within p85. Thus, the p85-mediated enhancement of MBP promoter activity in oligodendrocytes appears to be independent of PI3K activity and dependent on the adapter functions of the p85 subunit's SH2 domains.
authors.affiliation: Division of Basic Biomedical Sciences, University of South Dakota School of Medicine, 414 East Clark Street, Vermillion, SD 57069, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Clark
authors.forename: W Keith
authors.initials: WK
authors.lastname: Miskimins
authors.forename: Robin
authors.initials: R
authors.lastname: Miskimins
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D005799:Genes, Dominant; D004676:Myelin Basic Protein / Q000235:genetics*; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010744:Phosphoric Monoester Hydrolases / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000502:physiology*; D021122:Protein Subunits / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D018909:src Homology Domains / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D004676:Myelin Basic Protein; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010744:Phosphoric Monoester Hydrolases; D021122:Protein Subunits; D025521:Tumor Suppressor Proteins