npj Systems Biology and Applications,
Год журнала:
2024,
Номер
10(1)
Опубликована: Авг. 11, 2024
Ligand–receptor
systems,
covalent
modification
cycles,
and
transcriptional
networks
are
the
fundamental
components
of
cell
signaling
gene
expression
systems.
While
their
behavior
in
reaching
a
steady-state
regime
under
step-like
stimulation
is
well
understood,
response
repetitive
stimulation,
particularly
at
early
time
stages
poorly
characterized.
Yet,
early-stage
responses
to
external
inputs
arguably
as
informative
late-stage
ones.
In
simple
periodic
elicits
an
initial
transient
response,
followed
by
behavior.
Transient
relevant
when
has
limited
span,
or
stimulated
component's
timescale
slow
compared
timescales
downstream
processes,
which
case
latter
processes
may
be
capturing
only
those
transients.
this
study,
we
analyze
frequency
motifs
different
stages.
We
use
dose-conserved
pulsatile
input
signals
consider
metrics
versus
curves.
show
that
ligand–receptor
there
preference
some
specific
during
stages,
not
present
regime.
suggest
general
system-level
mechanism
cells
filter
have
consequences
for
higher
order
circuits.
addition,
evaluate
how
described
isolated
reflected
similar
types
cascades
pathways
they
part.
Our
studies
preferences
important
dynamic
features
been
overlooked.
Journal of Biological Chemistry,
Год журнала:
2022,
Номер
299(1), С. 102803 - 102803
Опубликована: Дек. 15, 2022
CCN5
is
a
divergent
member
of
the
cellular
communication
network
factor
(CCN)
family
in
that
it
lacks
carboxyl
terminal
cystine
knot
domain
common
to
other
CCN
members.CCN5
has
been
reported
antagonize
profibrotic
actions
CCN2
and
inhibit
myocardial
collagen
deposition
fibrosis
chronic
pressure
overload
heart.However,
what
mechanisms
regulate
activity
heart
remain
unknown.Recombinant,
replication
defective
adenovirus
encoding
firefly
luciferase
under
control
human
promoter
was
prepared
used
investigate
transcription
relevant
cells.Tissue
distribution
hearts
from
healthy
mice
subjected
infarction
investigated.Contrary
immediate
early
gene
CCN2,
we
find
induced
late
proliferation
maturation
phases
scar
healing.CCN5
identified
principally
endothelial
cells,
fibroblasts,
smooth
muscle
macrophages.Our
data
show
protein
levels
are
by
catecholamines
via
β
2
-adrenergic
receptors.Myocardial
induction
further
confirmed
isoproterenol-infused
mice.We
also
repressed
TNF-α,
an
inflammatory
mediator
highly
elevated
wound
healing
following
infarction.In
conclusion,
predominates
macrophages
differentiating
tissue
its
conversely
regulated
agonists
TNF-α.
Scientific Reports,
Год журнала:
2023,
Номер
13(1)
Опубликована: Июнь 10, 2023
The
extracellular
signal-regulated
kinase
(ERK)
is
a
serine/threonine
that
known
to
regulate
cellular
events
such
as
cell
proliferation
and
differentiation.
ERK
signaling
pathway
activated
by
fibroblast
growth
factors,
considered
be
indispensable
for
the
differentiation
of
primitive
endoderm
cells,
not
only
in
mouse
preimplantation
embryos,
but
also
embryonic
stem
(ESC)
culture.
To
monitor
activity
living
undifferentiated
differentiating
ESCs,
we
established
EKAREV-NLS-EB5
ESC
lines
stably
express
EKAREV-NLS,
biosensor
based
on
principle
fluorescence
resonance
energy
transfer.
Using
EKAREV-NLS-EB5,
found
exhibited
pulsatile
dynamics.
ESCs
were
classified
into
two
groups:
active
cells
showing
high-frequency
pulses,
inactive
demonstrating
no
detectable
pulses
during
live
imaging.
Pharmacological
inhibition
major
components
revealed
Raf
plays
an
important
role
determining
pattern
pulses.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Янв. 28, 2023
Summary
Fibroblast
growth
factors
(FGFs)
are
paracrine
or
endocrine
signaling
proteins
that,
activated
by
their
ligands,
elicit
a
wide
range
of
health
and
disease-related
processes,
such
as
cell
proliferation
the
epithelial-to-mesenchymal
transition
(EMT).
The
detailed
molecular
pathway
dynamics
that
coordinate
these
responses
have
remained
to
be
determined.
To
elucidate
these,
we
stimulated
MCF-7
breast
cancer
cells
with
either
FGF2,
FGF3,
FGF4,
FGF10,
FGF19.
Following
activation
receptor,
quantified
kinase
activity
44
kinases
using
targeted
mass
spectrometry
assay.
Our
system-wide
data,
supplemented
(phospho)proteomics
reveal
ligand-dependent
distinct
dynamics,
involvement
not
earlier
reported
MARK,
revise
some
effects
on
biological
outcomes.
In
addition,
logic-based
dynamic
modeling
kinome
further
verifies
goodness-of-fit
predicted
models
reveals
tight
regulation
RAF
family.
npj Systems Biology and Applications,
Год журнала:
2024,
Номер
10(1)
Опубликована: Авг. 11, 2024
Ligand–receptor
systems,
covalent
modification
cycles,
and
transcriptional
networks
are
the
fundamental
components
of
cell
signaling
gene
expression
systems.
While
their
behavior
in
reaching
a
steady-state
regime
under
step-like
stimulation
is
well
understood,
response
repetitive
stimulation,
particularly
at
early
time
stages
poorly
characterized.
Yet,
early-stage
responses
to
external
inputs
arguably
as
informative
late-stage
ones.
In
simple
periodic
elicits
an
initial
transient
response,
followed
by
behavior.
Transient
relevant
when
has
limited
span,
or
stimulated
component's
timescale
slow
compared
timescales
downstream
processes,
which
case
latter
processes
may
be
capturing
only
those
transients.
this
study,
we
analyze
frequency
motifs
different
stages.
We
use
dose-conserved
pulsatile
input
signals
consider
metrics
versus
curves.
show
that
ligand–receptor
there
preference
some
specific
during
stages,
not
present
regime.
suggest
general
system-level
mechanism
cells
filter
have
consequences
for
higher
order
circuits.
addition,
evaluate
how
described
isolated
reflected
similar
types
cascades
pathways
they
part.
Our
studies
preferences
important
dynamic
features
been
overlooked.
