cAMP and Activation

of CREB pathway

JACINTHA ESTHER
09HA062
cAMP
Secondary messenger

Derived from ATP

Required for intracellular signalling

(transfers the effect of hormones that cannot pass through

the membrane)
Most pathways are cAMP-dependent

Synthesized by adenylyl cyclase

Decomposed to AMP by phosphodiesterase

Main function of cAMP:
Activation of protein kinases
It also regulates the passage of Ca2+ through ion channels
Protein Kinase
Family of enzymes dependent on the level of cAMP
It is a holoenzyme with 4 subunits.
2 catalytic subunits and 2 regulatory subunits
Function:
It phosphorylates its substrate at the serine/threonine
residue by transferring terminal ATP phosphates.
2 effects of its catalysis:
- direct protein phosphorylation
-protein synthesis
Activation of CREB
What is CREB?

It is a transcription factor that binds to DNA sequences called

cAMP Response Element.

CREB-cAMP Response Element Binding protein

CREB regulates the transcription of genes like c-fos,

neurotrophin BNDF, tyrosine hydroxylase many

neuropeptides.
It has a basic leucine zipper domain (bZIP) by which it binds

to the DNA
CREB (bZIP domain)

DNA (CRE)
This CREB protein is activated by the active protein
kinase which was activated by cAMP.
Protein Kinase phosphorylates Ser-133 residue of
CREB thus activating it.
Thus cAMP plays a major role in activation of CREB
required for transcription of other proteins.
Now, the CREB binds to the DNA and it co-activated
by CBP (CREB Binding Protein) allowing it to switch
on/off the genes.
Multiple Signalling Pathway activating CREB
Function of CREB
CREB proteins in neurons are assumed to be involved
in formation of long-term memory.
It plays a important role in drug addiction.

Thus, disturbance of CREB contribute to Huntington’s

disease.
CREB is an important protein and cAMP plays an
important role in its activation.
THANK
YOU!!