Science,
Год журнала:
2004,
Номер
304(5678), С. 1800 - 1804
Опубликована: Май 25, 2004
Pathogenic
mycobacteria
resist
lysosomal
delivery
after
uptake
into
macrophages,
allowing
them
to
survive
intracellularly.
We
found
that
the
eukaryotic-like
serine/threonine
protein
kinase
G
from
pathogenic
was
secreted
within
macrophage
phagosomes,
inhibiting
phagosome-lysosome
fusion
and
mediating
intracellular
survival
of
mycobacteria.
Inactivation
by
gene
disruption
or
chemical
inhibition
resulted
in
localization
mycobacterial
cell
death
infected
macrophages.
Besides
identifying
a
target
for
control
infections,
these
findings
suggest
have
evolved
signal
transduction
mechanisms
capable
modulating
host
trafficking
pathways.
Cancer Research,
Год журнала:
2007,
Номер
67(24), С. 11924 - 11932
Опубликована: Дек. 15, 2007
Abstract
Epidermal
growth
factor
receptor
(EGFR)
tyrosine
kinase
inhibitors
gefitinib
and
erlotinib
are
effective
treatments
for
a
subset
of
non–small
cell
lung
cancers.
In
particular,
cancers
with
specific
EGFR-activating
mutations
seem
to
be
the
most
sensitive
these
agents.
However,
despite
their
initial
response,
such
almost
invariably
develop
resistance.
50%
cancers,
secondary
EGFR
mutation,
T790M,
has
been
identified
that
renders
ineffective
activity.
Thus,
there
is
clinical
need
novel
can
effectively
inactivate
T790M-containing
proteins.
this
study,
we
evaluate
effectiveness
compound,
PF00299804,
an
irreversible
pan-ERBB
inhibitor.
The
results
from
studies
show
PF00299804
potent
inhibitor
as
well
T790M
resistance
mutation
both
in
vitro
vivo.
Additionally,
highly
wild-type
ERBB2
gefitinib-resistant
oncogenic
These
preclinical
evaluations
support
further
development
and/or
amplifications
ERBB
family
members.
[Cancer
Res
2007;67(24):11924–32]
Physiological Reviews,
Год журнала:
2010,
Номер
90(4), С. 1507 - 1546
Опубликована: Окт. 1, 2010
Among
the
myriad
of
intracellular
signaling
networks
that
govern
cardiac
development
and
pathogenesis,
mitogen-activated
protein
kinases
(MAPKs)
are
prominent
players
have
been
focus
extensive
investigations
in
past
decades.
The
four
best
characterized
MAPK
subfamilies,
ERK1/2,
JNK,
p38,
ERK5,
targets
pharmacological
genetic
manipulations
to
uncover
their
roles
development,
function,
diseases.
However,
information
reported
literature
from
these
efforts
has
not
yet
resulted
a
clear
view
about
specific
pathways
heart.
Rather,
controversies
contradictive
results
led
perception
MAPKs
ambiguous
characters
heart
with
both
protective
detrimental
effects.
primary
object
this
review
is
provide
comprehensive
overview
current
progress,
an
effort
highlight
areas
where
consensus
established
verses
ones
controversy
remains.
hypertrophy,
ischemia/reperfusion
injury,
pathological
remodeling
main
focuses
as
represent
most
critical
issues
for
evaluating
viable
therapeutic
development.
studies
presented
will
help
reveal
major
challenges
field
limitations
approaches
point
need
future
gain
better
understanding
fundamental
mechanisms
function
regulation
Redox Biology,
Год журнала:
2015,
Номер
6, С. 51 - 72
Опубликована: Июль 5, 2015
Transcription
factors
of
the
forkhead
box,
class
O
(FoxO)
family
are
important
regulators
cellular
stress
response
and
promote
antioxidant
defense.
On
one
hand,
FoxOs
stimulate
transcription
genes
coding
for
proteins
located
in
different
subcellular
compartments,
such
as
mitochondria
(i.e.
superoxide
dismutase-2,
peroxiredoxins
3
5)
peroxisomes
(catalase),
well
found
extracellularly
plasma
(e.g.,
selenoprotein
P
ceruloplasmin).
other
reactive
oxygen
species
(ROS)
stressful
stimuli
that
elicit
formation
ROS,
may
modulate
FoxO
activity
at
multiple
levels,
including
posttranslational
modifications
(such
phosphorylation
acetylation),
interaction
with
coregulators,
alterations
localization,
protein
synthesis
stability.
Moreover,
transcriptional
posttranscriptional
control
expression
is
sensitive
to
ROS.
Here,
we
review
these
aspects
biology
focusing
on
redox
regulation
signaling,
emphasis
interplay
between
ROS
under
various
physiological
pathophysiological
conditions.
Of
particular
interest
dual
role
played
by
cancer
development
their
key
whole
body
nutrient
homeostasis,
modulating
metabolic
adaptations
and/or
disturbances
low
vs.
high
intake.
Examples
discussed
here
include
calorie
restriction
starvation
adipogenesis,
obesity
type
2
diabetes.
