Protein kinase A
Protein Kinase A (PKA) is a protein that is dependent on cyclic AMP (cAMP) and without it, is deactivated. PKA is involved in signal-transduction pathways and phosphorylates proteins by adding a phosphate group. The molecule consists of two subunits, a regulatory subunit and a calalytic subunit [1]. These subunits are inactive when cAMP is not bound. When cAMP binds to a regulatory subunit a conformational change occurs. This change means that the catalytic subunit becomes active and is no longer inhibited. This means that the protein can now phosphorylate other proteins by removing a phosphate from ATP, and adding it to a serine residue on the target protein which in turn leads to a cellular response [2].
Protein Kinase A (PKA) is one of the member of family of enyzmes which is functionally dependent on the levels of cyclic-adenomonophopshate (cAMP). It is also commonly known as the cAMP dependent A kinase, therefore it works through the cAMP signalling pathway. Essentially, PKA is responsible for all the cellular responses induced by cAMP second messenger system.
Structure:
PKA is a heterotetramer consists of 4 subunits, of which composed of 2 regulatory and 2 catalytic subunits.
- Regulatory subunit: Two of these subunits are joined together covalently via disulfide bonds. Each subunit has 2 cAMP binding sites, a domain that interacts with the catalytic subunit and a "auto-inhibitory" domain that act as a pseudo-substrate motif RRGA1 for the catalytic subunit. Two major forms of regulatory subunits exist, RI and RII, each form has two subtypes alpha and beta, while each isotype is encoded by different genes.
- Catalytic subunit: This subunit contains the ATP binding domain and the enzyme's active site. Each subunit is bound to the either side of the regulatory subunit. There are three isotypes which have been identified for the catalytic subunit(alpha beta and gamma).
Regulation of activity:
When cAMP levels are low, the catalytic subunits are bound to the regulatoy subunit dimer and are inactive. As the concentration of cAMP increases, cAMP molecules bind to the regulatory subunits, causing a conformational change of the catalytic subunits from an inactive toa n active form.
References
- ↑ Berg, J. Tymoczko, J. and Stryer, L. (2007) Biochemistry, 6th edition, New York: WH Freeman
- ↑ http://www.vivo.colostate.edu/hbooks/molecules/pka.html
R. Bowen, November 28 2003
Hypertexts for Biomedical Sciences, Colorado State University