Dieter Kaufmann, Iska Junge, Britta Bartelt, Herbert Lattke, Ralf Müller
On the Lysosomal Degradation of Neurofibromin and Its
Phosphorylation in Cultured Melanocytes
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.
Biological Chemistry, Walter de Gruyter
Print ISSN: 1431-6730
Volume: 380, 09/1999
Pages: 1071 - 1078
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