CAMP-dependent protein kinase

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The correct title of this article is cAMP-dependent protein kinase. The initial letter is shown 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 catalyze 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

[edit] Regulation

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.