They won the Nobel Prize in Physiology or Medicine in 1992 for their work on phosphorylation and dephosphorylation and how it relates to PKA activity.

[5] The following human genes encode PKA subunits: PKA is also commonly known as cAMP-dependent protein kinase, because it has traditionally been thought to be activated through release of the catalytic subunits when levels of the second messenger called cyclic adenosine monophosphate, or cAMP, rise in response to a variety of signals.

However, recent studies evaluating the intact holoenzyme complexes, including regulatory AKAP-bound signalling complexes, have suggested that the local sub cellular activation of the catalytic activity of PKA might proceed without physical separation of the regulatory and catalytic components, especially at physiological concentrations of cAMP.

[6][7] In contrast, experimentally induced supra physiological concentrations of cAMP, meaning higher than normally observed in cells, are able to cause separation of the holoenzymes, and release of the catalytic subunits.

[6] Extracellular hormones, such as glucagon and epinephrine, begin an intracellular signalling cascade that triggers protein kinase A activation by first binding to a G protein–coupled receptor (GPCR) on the target cell.

[7][10] Below is a list of the steps involved in PKA activation: The liberated catalytic subunits can then catalyze the transfer of ATP terminal phosphates to protein substrates at serine, or threonine residues.

In the active conformation, the C helix packs against the N-terminal lobe and the Aspartate residue of the conserved DFG motif chelates the Mg2+ ions, assisting in positioning the ATP substrate.

There are several conserved residues, include Glutamate (E) 91 and Lysine (K) 72, that mediate the positioning of alpha- and beta-phosphate groups.

Downregulation of protein kinase A occurs by a feedback mechanism and uses a number of cAMP hydrolyzing phosphodiesterase (PDE) enzymes, which belong to the substrates activated by PKA.

PKA helps transfer/translate the dopamine signal into cells in the nucleus accumbens, which mediates reward, motivation, and task salience.

The vast majority of reward perception involves neuronal activation in the nucleus accumbens, some examples of which include sex, recreational drugs, and food.

Protein Kinase A signal transduction pathway helps in modulation of ethanol consumption and its sedative effects.

A mouse study reports that mice with genetically reduced cAMP-PKA signalling results into less consumption of ethanol and are more sensitive to its sedative effects.