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ERK1/2 signaling is essential for the chemoattraction exerted by human FGF2 and human anosmin-1 on newborn rat and mouse OPCs via FGFR1.
[kallmann syndrome]
Signaling
through
fibroblast
growth
factor
receptors
(
FGFRs
)
is
essential
for
many
cellular
processes
including
proliferation
and
migration
,
as
well
as
differentiation
events
such
as
myelination
.
Anosmin-
1
is
an
extracellular
matrix
(
ECM
)
glycoprotein
that
interacts
with
the
fibroblast
growth
factor
receptor
1
(
FGFR
1
)
to
exert
its
biological
actions
through
this
receptor
,
although
the
intracellular
pathways
underlying
anosmin-
1
signaling
remain
largely
unknown
.
This
protein
is
defective
in
the
X-
linked
form
of
Kallmann
syndrome
(
KS
)
and
has
a
prominent
role
in
the
migration
of
neuronal
and
oligodendroglial
precursors
.
We
have
shown
that
anosmin-
1
exerts
a
chemotactic
effect
via
FGFR
1
on
neuronal
precursors
from
the
subventricular
zone
(
SVZ
)
and
the
essential
role
of
the
ERK
1
/
2
signaling
.
We
report
here
the
positive
chemotactic
effect
of
FGF
2
and
anosmin-
1
on
rat
and
mouse
postnatal
OPCs
via
FGFR
1
.
The
same
effect
was
observed
with
the
truncated
N-
terminal
region
of
anosmin-
1
(
A
1
Nt
)
.
The
introduction
in
anosmin-
1
of
the
missense
mutation
F
5
17
L
found
in
patients
suffering
from
KS
annulled
the
chemotactic
activity
;
however
,
the
mutant
form
carrying
the
disease-causing
mutation
E
514
K
also
found
in
KS
patients
,
behaved
as
the
wild-
type
protein
.
The
chemoattraction
exhibited
by
FGF
2
and
anosmin-
1
on
OPCs
was
blocked
by
the
mitogen-activated
protein
kinase
(
MAPK
)
inhibitor
U
0126
,
suggesting
that
the
activation
of
the
ERK
1
/
2
MAPK
signaling
pathway
following
interaction
with
the
FGFR
1
is
necessary
for
FGF
2
and
anosmin-
1
to
exert
their
chemotactic
effect
.
In
fact
,
both
proteins
were
able
to
induce
the
phosphorylation
of
the
ERK
1
/
2
kinases
after
the
activation
of
the
FGFR
1
receptor
.
Diseases
Validation
Diseases presenting
"growth factor receptor"
symptom
achondroplasia
aromatase deficiency
cholangiocarcinoma
dedifferentiated liposarcoma
esophageal adenocarcinoma
esophageal carcinoma
esophageal squamous cell carcinoma
kallmann syndrome
lymphangioleiomyomatosis
oral submucous fibrosis
proteus syndrome
severe combined immunodeficiency
wiskott-aldrich syndrome
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