Protein Kinase A


Structure

PKA.jpg
Fig. 1. Crystal Structure of PKA with Inhibitor Compound 36. Zeng, Q., et al. (2010). Bioorganic & Medicinal Chemistry Letters. 20, 1559-1564.

PKA contains a dimer of regulatory subunits bound to two catalytic subunits. In this holoenzyme form, the catalytic subunits are rendered inactive. In the active form, the regulatory dimer releases the catalytic subunits and they become functional.[1]

Function

PKA uses its two catalytic subunits to phosphorylate of a wide range of enzymes utilizing the terminal phosphate of an ATP molecule. It specifically targets serine/threonine residues. This is a method of covalent modification that may lead to activation or inactivation depending on the target.[1]

Regulation

PKA is also known as cAMP-dependant protein kinase because concentration levels of cAMP lead to activation or inactivation of the kinase.
High [cAMP] conditions: four cAMP molecules bind to PKA’s regulatory subunits (two per subunit) causing them to release the catalytic subunits rendering them active.Low [cAMP] conditions: the regulatory subunits are not bound by cAMP and are left inhibiting the catalytic subunits.[1]

Relevance to Lipolysis

PKA phosphorylates hormone sensitive lipase (HSL) and acetyl-CoA carboxylase (ACC). For HSL, phosphorylation leads to activation; while, for ACC it leads to deactivation.[2]

Pathway 1
| Previous Page: Adenyl Cyclase | Current Page | Next Page: Hormone Sensitive Lipase |

Pathway 2
| Previous Page: Phosphodiesterase | Current Page | Next Page: ACC |

  1. ^ Manni, S., Mauban, J.H., Ward, C.W., Bond, M. (2008). J. Biol. Chem. 283(35), 24145-24154
  2. ^ Hursel, R., Westerterp-Plantenga, M.S. (2010). International Journal of Obesity. 34, 659-669