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The title of this article should be cAMP-dependent protein kinase. The initial letter is capitalized due to technical restrictions.

In cell biology, cAMP-dependent protein kinase (cAPK), also known as protein kinase A (PKA, EC 2.7.11.11), refers to a family of enzymes whose activity is dependent on the level of cyclic AMP (cAMP) in the cell.

Each PKA is a holoenzyme that consists of two regulatory and two catalytic subunits. Under low levels of cAMP, the holoenzyme remains intact and is catalytically inactive. When the concentration of cAMP rises (e.g. activation of adenylate cyclases by certain G protein-coupled receptors, inhibition of phosphodiesterases which degrade cAMP), cAMP binds to the two binding sites on the regulatory subunits, which then undergo a conformational change that releases the catalytic subunits. The free catalytic subunits can then catalyse the transfer of ATP terminal phosphates to protein substrates at serine, or threonine residues. This phosphorylation usually results in a change in activity of the substrate. Since PKAs are present in a variety of cells and act on different substrates, PKA and cAMP regulation are involved in many different pathways. In addition, the effects of PKA phosphylation are generally transient because protein phosphatases quickly dephosphorylate PKA targets

Regulation Edit

Protein kinase A has several functions in the cell, including regulation of glycogen, sugar, and lipid metabolism. It is controlled by cAMP: in the absence of cAMP, the kinase is a tetramer of two regulatory and two catalytic subunits (R₂C₂), with the regulatory subunits blocking the catalytic center of the catalytic subunits. Binding of cAMP to the regulatory subunit leads to dissociation of active RC dimers. Also, the catalytic subunit itself can be regulated by phosphorylation.

Downregulation of protein kinase A occurs by a feedback mechanism: one of the substrates that is activated by the kinase is a phosphodiesterase, which converts cAMP to AMP, thus reducing the amount of cAMP that can activate protein kinase A.

PKA and Metabolism Edit

Insulin and glucagon both affect the activity of protein kinase A, by changing the levels of cAMP in a cell via the G-protein mechanism (insulin signals via a tyrosine kinase), using adenylate cyclase. Protein Kinase A acts to phosphorylate many enzymes important in metabolism. Protein kinase A phosphorylates Acetyl-CoA carboxylase and pyruvate dehydrogenase. Allosteric regulation of these enzymes in such a manner has an inhibitory effect. Insulin will increase the level of phosphorylation of these enzymes, which will divert acetyl-coA down the lipogenesis pathway. Glucagon has an anatagonistic effect.

PKA and Dopamine Edit

PKA helps transfer/translate the dopamine signal into cells. It has been found (postmortem) to be elevated in the brains of smokers, in the nucleus accumbens, which mediates reward and motivation: a part of the brain acted on by "virtually all" recreational drugs; as well as "in the area of the midbrain that responds to dopamine, which acts as a 'reward chemical' in smokers and former smokers." ^[1]

See alsoEdit

• Protein kinase
• Signal transduction
• G protein-coupled receptor
• Serine/threonine-specific protein kinase
• Myosin light-chain kinase

ReferencesEdit

1. ↑ http://news.bbc.co.uk/2/hi/health/6378179.stm

External linksEdit

• MeSH Cyclic+AMP-Dependent+Protein+Kinases

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