Abstract
In this paper we address the linking of platelet-derived growth factor (PDGF) and basic fibroblast growth factor (FGF-2) to intracellular signaling molecules in oligodendrocyte progenitors. It is demonstrated that both growth factors activate downstream targets similar to those shown for protein kinase C (PKC) activation. Yet, neither the arrest of terminal oligodendrocyte differentiation nor the proliferation induced by PDGF or FGF-2 can be antagonized by inhibition of PKC. Rather, p42/p44 mitogen-activated protein kinase (MAPK), p38 MAPK, and pp70 S6 kinase were found to be necessary for the mitogenic activity of PDGF and FGF-2. Paradoxically, these kinases were also necessary for the onset of oligodendrocyte differentiation in control cells. In addition, cAMP-dependent kinase A (PKA) activation inhibited the mitogenic response of oligodendrocyte progenitors to FGF-2. Taken together, the molecular mechanism that controls oligodendrocyte lineage progression is operated by at least two signal pathways, which interfere either with proliferation and/or differentiation of oligodendrocyte progenitors.
Copyright 2000 Academic Press.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Differentiation / drug effects
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Cell Division / drug effects
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Cyclic AMP / physiology
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Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
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Cyclic AMP-Dependent Protein Kinases / physiology
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Enzyme Inhibitors / pharmacology
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Estrenes / pharmacology
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Fibroblast Growth Factor 2 / pharmacology*
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Flavonoids / pharmacology
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Genistein / pharmacology
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Imidazoles / pharmacology
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Intracellular Signaling Peptides and Proteins*
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MAP Kinase Signaling System / drug effects
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Membrane Proteins*
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Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
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Mitogen-Activated Protein Kinase 1 / physiology
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Mitogen-Activated Protein Kinases / antagonists & inhibitors
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Mitogen-Activated Protein Kinases / physiology
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Myristoylated Alanine-Rich C Kinase Substrate
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Nerve Tissue Proteins / physiology
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Oligodendroglia / drug effects*
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Oligodendroglia / physiology
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Phosphorylation
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Platelet-Derived Growth Factor / pharmacology*
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Protein Kinase C / antagonists & inhibitors
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Protein Kinase C / physiology
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Protein Processing, Post-Translational
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Proteins / metabolism
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Pyridines / pharmacology
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Pyrrolidinones / pharmacology
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Rats
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Ribosomal Protein S6 Kinases / antagonists & inhibitors
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Ribosomal Protein S6 Kinases / physiology
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Signal Transduction / drug effects*
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Sirolimus / pharmacology
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Stem Cells / drug effects*
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Stem Cells / physiology
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p38 Mitogen-Activated Protein Kinases
Substances
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Enzyme Inhibitors
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Estrenes
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Flavonoids
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Imidazoles
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Nerve Tissue Proteins
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Platelet-Derived Growth Factor
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Proteins
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Pyridines
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Pyrrolidinones
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Fibroblast Growth Factor 2
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1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
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Myristoylated Alanine-Rich C Kinase Substrate
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Genistein
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Cyclic AMP
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Ribosomal Protein S6 Kinases
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Cyclic AMP-Dependent Protein Kinases
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Protein Kinase C
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases
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SB 203580
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
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Sirolimus