Protein Kinase A- Cyclic AMP

Running head: PROTEIN KINASE A- CYCLIC AMP
PROTEIN KINASE A- CYCLIC AMP
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PROTEIN KINASE A- CYCLIC AMP
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Protein kinase A- Cyclic AMP
Cyclic AMP-dependent protein kinase (PKA) is the signalling molecule which is known
to play key role in cellular process. Protein kinase A is dependent on cyclic AMP for signal
transduction. PKA stimulate the signal transduction pathway by phosphorylating the proteins.
The ligand of the enzyme is Cyclic AMP, which is responsible for activation of PKA and thereby
the signal cascade.
PKA is a holoenzyme complex which is composed of four subunits, two catalytic (C)
and two regulatory (R) subunits. These subunits are joined by disulphide bond. PKA is generally
located at the cytoplasm or it may be associated with the different organelle or cellular structure
depending on the type of regulation of PKA (Del Rio, Nielsen and Taylor 2017). It is anchored
with the help of A kinase anchor protein (AKAPs) in specific location. Major stimulator of PKA
is cAMP which acts as a second messenger. It is generated in response of GPCR protein by
activation of Adenylate Cyclase (Autenrieth et al. 2016). Such response is triggered by hormone
like glucagon.
R subunit have two cyclic AMP binding sites, which is auto-inhibitory domain that tend
to mimic pseudo-substrate motif RRGA1 for catalytic subunit. The catalytic subunit have ATP
binding domain with active binding site. Each of the (C) subunit is bounded with the regulatory
subunit via vanderwal interaction. cAMP binds at the R subunit and the complex undergo
conformational changes which causes its dissociation from C subunit. The activated C subunit
phosphorylates various metabolic enzymes and affects its signalling pathways in cell. Recent
studies suggest that PKA can get activated by sub cellular activation without physical separation
of the subunits (Eichel and von Zastrow 2018).