Home

cAMPPKACREB

cAMPPKACREB refers to the signaling axis that links cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), and the cAMP response element-binding protein (CREB). This module translates extracellular signals into transcriptional changes by a cascade that is central to many physiological processes, especially in the nervous system.

Mechanism: Activation often begins with extracellular ligands binding to G protein-coupled receptors, stimulating adenylyl cyclase to

Regulation: cAMP levels are tightly controlled by phosphodiesterases that degrade cAMP and by phosphatases that reverse

Functions and significance: The cAMP/PKA/CREB axis influences learning and memory, neuronal development, metabolism, and stress responses.

See also: CREB, PKA, cAMP signaling, CBP/p300, CRE elements.

synthesize
cAMP.
The
rise
in
cAMP
binds
to
the
regulatory
subunits
of
PKA,
releasing
its
catalytic
subunits.
The
active
PKA
catalytic
subunits
translocate
to
the
nucleus
and
phosphorylate
CREB
at
specific
serine
residues
(most
notably
Ser133).
Phosphorylated
CREB
recruits
the
coactivator
CBP/p300,
forming
a
transcriptional
complex
that
binds
to
cAMP
response
elements
(CRE)
in
target
gene
promoters,
initiating
transcription
of
genes
such
as
c-Fos,
BDNF,
and
others
involved
in
synaptic
plasticity
and
survival.
CREB
phosphorylation.
Cross-talk
with
other
signaling
pathways
(e.g.,
MAPK,
calcium
signaling)
modulates
the
strength
and
duration
of
the
response.
Dysregulation
has
been
associated
with
cognitive
disorders,
mood
disorders,
addiction,
and
metabolic
diseases
in
various
contexts.
Pharmacological
targeting
of
components
of
this
pathway,
including
PDE
inhibitors
or
modulators
of
CREB
activity,
remains
an
area
of
research.