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Protein kinase A

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Redirected from Function of cAMP-dependent protein kinase



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

In cell biology, Protein kinase A (PKA) is a family of enzymes whose activity is dependent on cellular levels of cyclic AMP (cAMP). PKA is also known as cAMP-dependent protein kinase (EC Protein kinase A has several functions in the cell, including regulation of glycogen, sugar, and lipid metabolism.

It should be confused neither with AMP-activated protein kinase - which, although being of similar nature, may have opposite effects -[1] nor with cyclin-dependent kinases (Cdks), nor with the acid dissociation constant pKa.




Each PKA is a holoenzyme that consists of a regulatory subunit dimer, with each regulatory subunit being bound to a catalytic subunit. 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 G protein-coupled receptors coupled to Gs, inhibition of phosphodiesterases that degrade cAMP), cAMP binds to the two binding sites on the regulatory subunits, which leads to the release of the catalytic subunits. For maximal function, each catalytic subunit must also be phosphorylated, which occurs on Thr 197 and helps orientate catalytic residues in the active site.[2]

1. Cytosolic cAMP increases 2. Two cAMP molecules bind to each PKA regulatory subunit 3. The regulatory subunits move out of the active sites of the catalytic subunits and the R2C2 complex dissociates 4. The free catalytic subunits interact with proteins to phosphorylate Ser or Thr residues.


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 regulation and cAMP regulation are involved in many different pathways.



Inactivation Edit




Anchorage Edit

The regulatory subunit dimer of PKA is important for localizing the kinase inside the cell. The dimerization and docking (D/D) domain of the dimer binds to the A-kinase binding (AKB) domain of A-kinase anchor protein (AKAP). The AKAPs localize PKA to various locations (e.g., plasma membrane, mitochondria, etc.) within the cell.

AKAPs bind many other signaling proteins, creating a very efficient signaling hub at a certain location within the cell. For example, an AKAP located near the nucleus of a heart muscle cell would bind both PKA and phosphodiesterase (hydrolyzes cAMP), which allows the cell to limit the productivity of PKA, since the catalytic subunit is activated once cAMP binds to the regulatory subunits.


PKA phosphorylates proteins that have the motif Arginine-Arginine-X-Serine exposed, in turn (de)activating the proteins. As protein expression varies from cell type to cell type, the proteins that are available for phosphorylation will depend upon the cell in which PKA is present. Thus, the effects of PKA activation vary with cell type:

Overview tableEdit

Cell type Organ/system Stimulators
ligands --> Gs-GPCRs
or PDE inhibitors
ligands --> Gi-GPCRs
or PDE stimulators
myocyte (skeletal muscle) muscular system
myocyte (cardiac muscle) muscular system
hepatocyte liver
principal cells in kidney kidney
myocyte (smooth muscle) muscular system Vasodilation
Inner medullary collecting duct cell kidney Vasopressin --> V2 receptor
juxtaglomerular cell kidney renin secretion

In adipocytes and hepatocytes Edit


In nucleus accumbens neuronsEdit


See alsoEdit


  1. Hallows KR, Alzamora R, Li H, et al. (April 2009). AMP-activated protein kinase inhibits alkaline pH- and PKA-induced apical vacuolar H+-ATPase accumulation in epididymal clear cells. Am. J. Physiol., Cell Physiol. 296 (4): C672–81.
  2. Voet, Voet & Pratt (2006). Fundamentals of Biochemistry. Wiley. Pg 492
  3. 3.0 3.1 3.2 3.3 3.4 Rang, H. P. (2003). Pharmacology, Edinburgh: Churchill Livingstone. Page 172
  4. Rodriguez P, Kranias EG. (December 2005). Phospholamban: a key determinant of cardiac function and dysfunction.. Arch Mal Coeur Vaiss 98 (12): 1239–43.
  5. 5.0 5.1 5.2 5.3 5.4 Walter F., PhD. Boron. Medical Physiology: A Cellular And Molecular Approaoch, Elsevier/Saunders. Page 842
  8. 8.0 8.1 8.2 8.3 Walter F., PhD. Boron (2003). Medical Physiology: A Cellular And Molecular Approaoch, 1300, Elsevier/Saunders. Page 867
  9. includeonly>"Smoking alters brain 'like drugs'", BBC News, 2007-02-24. Retrieved on 2010-05-22.

External linksEdit

de:Proteinkinase A

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