Science,
Journal Year:
2013,
Volume and Issue:
339(6125), P. 1323 - 1328
Published: Feb. 22, 2013
Coordinating
Metabolism
Growth
factors
help
to
coordinate
metabolism
with
growth
in
part
by
stimulating
the
activity
of
protein
kinase
mTORC1
(mechanistic
target
rapamycin
complex
1).
Ben-Sahra
et
al.
(p.
1323
,
published
online
21
February)
and
Robitaille
1320
independently
identified
a
key
mTORC1—carbamolyl-phosphate
synthase
2,
or
CAD,
rate-limiting
enzyme
for
de
novo
synthesis
pyrimidines.
Metabolomic
profiling
phosphoproteomic
analyses
normal
cells
lacking
signaling
converged
on
CAD
as
point
at
which
growth-promoting
signals
also
ramp
up
production
nucleic
acids.
Cold Spring Harbor Perspectives in Biology,
Journal Year:
2014,
Volume and Issue:
6(1), P. a009191 - a009191
Published: Jan. 1, 2014
Jérémie
Boucher1,2,
André
Kleinridders1,2
and
C.
Ronald
Kahn1
1Section
on
Integrative
Physiology
Metabolism,
Joslin
Diabetes
Center
Department
of
Medicine,
Brigham
Women's
Hospital
Harvard
Medical
School,
Boston,
Massachusetts
02115
Correspondence:
c.ronald.kahn{at}joslin.harvard.edu
↵2
These
authors
contributed
equally
to
this
article.
Biochemical Journal,
Journal Year:
2011,
Volume and Issue:
441(1), P. 1 - 21
Published: Dec. 14, 2011
The
ribosomal
protein
S6K
(S6
kinase)
represents
an
extensively
studied
effector
of
the
TORC1
[TOR
(target
rapamycin)
complex
1],
which
possesses
important
yet
incompletely
defined
roles
in
cellular
and
organismal
physiology.
functions
as
environmental
sensor
by
integrating
signals
derived
from
diverse
cues
to
promote
anabolic
inhibit
catabolic
functions.
mTORC1
(mammalian
TORC1)
phosphorylates
activates
S6K1
S6K2,
whose
first
identified
substrate
was
rpS6
(ribosomal
S6),
a
component
40S
ribosome.
Studies
over
past
decade
have
uncovered
number
additional
substrates,
revealing
multiple
levels
at
mTORC1–S6K1
axis
regulates
cell
results
thus
far
indicate
that
controls
fundamental
processes,
including
transcription,
translation,
lipid
synthesis,
growth/size
metabolism.
In
present
review
we
summarize
regulation
S6Ks,
their
substrates
functions,
integration
within
rapidly
expanding
mTOR
TOR)
signalling
networks.
Although
our
understanding
role
physiology
remains
its
infancy,
evidence
indicates
this
controls,
least
part,
glucose
homoeostasis,
insulin
sensitivity,
adipocyte
metabolism,
body
mass
energy
balance,
tissue
organ
size,
learning,
memory
aging.
As
dysregulation
contributes
disease
states,
improved
function
networks
may
enable
development
novel
therapeutics.
Molecular Cancer,
Journal Year:
2023,
Volume and Issue:
22(1)
Published: Aug. 18, 2023
Abstract
The
PI3K/AKT/mTOR
(PAM)
signaling
pathway
is
a
highly
conserved
signal
transduction
network
in
eukaryotic
cells
that
promotes
cell
survival,
growth,
and
cycle
progression.
Growth
factor
signalling
to
transcription
factors
the
PAM
axis
regulated
by
multiple
cross-interactions
with
several
other
pathways,
dysregulation
of
can
predispose
cancer
development.
most
frequently
activated
human
often
implicated
resistance
anticancer
therapies.
Dysfunction
components
this
such
as
hyperactivity
PI3K,
loss
function
PTEN,
gain-of-function
AKT,
are
notorious
drivers
treatment
disease
progression
cancer.
In
review
we
highlight
major
dysregulations
cancer,
discuss
results
AKT
mTOR
inhibitors
monotherapy
co-administation
antineoplastic
agents
clinical
trials
strategy
for
overcoming
resistance.
Finally,
mechanisms
targeted
therapies,
including
immunology
immunotherapies
also
discussed.
