On the Lysosomal Degradation of Neurofibromin and Its Phosphorylation in Cultured Melanocytes
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Dieter Kaufmann
Abstract
Neurofibromatosis type 1 (NF1) is one of the most common inherited disorders in humans. Most of the NF1gene mutations result in a reduction of the amount of neurofibromin to about 50%. Recently, we found that the level of neurofibromin can be regulated posttranslationally through the alteration of its half-life. Here, we investigated whether lysosomes are involved in this post-translational regulation in cultured melanocytes of NF1 patients and controls. When the lysosomal degradation was inhibited by chloroquine, an increase of neurofibromin by a factor of 2 to 3, correlating with an increased half-life, was measured. Incubation with phosphoprotein-phosphatase inhibitors also increased the neurofibromin content in melanocytes. Investigations on phosphorylation of neurofibromin revealed a basal phosphorylation in melanocytes cultured with growth factor-deprived medium that increased upon incubation with the growth stimulators PMA or bFGF. Because both factors are also able to increase the half-life of neurofibromin, we suggest its phosphorylation to be an important step in protecting neurofibromin against specific lysosomal degradation.
Copyright © 1999 by Walter de Gruyter GmbH & Co. KG
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Articles in the same Issue
- Execution of Apoptosis: Converging or Diverging Pathways?
- Two Highly Related Homeodomain Proteins, Nkx5-1 and Nkx5-2, Display Different DNA Binding Specificities
- The Janus Face of the Archaeal Cdc48/p97 Homologue VAT: Protein Folding versus Unfolding
- Functional Characterization of an Extremely Thermophilic ATPase in Membranes of the Crenarchaeon Acidianus ambivalens
- On the Lysosomal Degradation of Neurofibromin and Its Phosphorylation in Cultured Melanocytes
- Rat Muscle Fructose-1,6-Bisphosphatase: Cloning of the cDNA, Expression of the Recombinant Enzyme, and Expression Analysis in Different Tissues
- Catalase-Peroxidase from the Cyanobacterium Synechocystis PCC 6803: Cloning, Overexpression in Escherichia coli, and Kinetic Characterization
- Expression of Plasma Prekallikrein mRNA in Human Nonhepatic Tissues and Cell Lineages Suggests Special Local Functions of the Enzyme
- Biochemical Characterization of the Catalytic Domain of Membrane-Type 4 Matrix Metalloproteinase
- Fluorometric Microassays for the Determination of Cathepsin L and Cathepsin S Activities in Tissue Extracts
- The Role of Protein Phosphatase 2A Catalytic Subunit Cα in Embryogenesis: Evidence from Sequence Analysis and Localization Studies
- DNA Binding of Myc/Max/Mad Network Complexes to Oligonucleotides Containing Two E Box Elements: c-Myc/Max Heterodimers Do Not Bind DNA Cooperatively
- Tight Interaction between Densely Methylated DNA Fragments and the Methyl-CpG Binding Domain of the Rat MeCP2 Protein Attached to a Solid Support
- Molecular Characterization of a Novel Mammalian DnaJ-Like Sec63p Homolog
