AC CAMP PKA Signaling Module

AC/cAMP/PKA Signaling Module (Overview)

adenylyl cyclase or AC for short, is a trans membrane protein.

The cytosolic region of adenylyl cyclase acts as an enzyme to catalyze synthesis of cyclic AMP, or cAMP from ATP.

• Cyclic AMP can bind to and regulate protein effectors.

Activation of Adenylyl Cyclase

One way that adenylyl cyclase can be activated is by binding of a GTP bound G alpha subunit of a heterotrimeric G protein.

The specific type of G alpha that binds to adenylyl cyclase is called a stimulatory G protein, or G alpha S because it stimulates the activity of the adenylyl cyclase.

Phosphodiesterase (PDE)

Phosphodiesterase are enzymes that oppose activity of adenylyl cyclase.

phosphodiesterase promotes destruction of cyclic AMP by catalyzing hydrolysis of a phosphodiesterase bond resulting in the conversion of cyclic AMP to AMP.

Protein Kinase A (PKA) Structure and Activation

One major target of cyclic AMP is protein kinase A or PKA, a serine threonine kinase

two regulatory subunits represented here by purple rectangles and two catalytic subunits, represented here by green circles associate together to form an inactive PKA complex.

When two molecules of cyclic AMP bind to each of the regulatory subunits, the catalytic subunits are released and each molecule can phosphorylate target protein effectors.

CREB (cAMP Response Element Binding Protein)

One potential target of active PKA catalytic subunits is the cyclic AMP response element binding protein, or CREB

CREB binds to a specific DNA sequence found near some target genes.

Phosphorylation of CREB leads to target gene expression