Part I. Introduction

Proteins undergo a huge number of post translational modifications. However, only a subset of these modifications are reversible, covalent modifications such as acetylation, fatty acid acylation, glycosylation and phosphorylation. These modifications affect the activity, life span, or cellular location of the modified proteins.

Of the post translational modifications mentioned above, phosphorylation is an important and ubiquitous one. Approximately 10% of the proteins in the cell cytosol is phosphorylated. The phosphorylation reaction in the cell is a reversible one where kinases catalyze the addition of the phosphoryl group and phosphatases catalyze the removal of the phosphoryl group. The reaction involves ATP as the phosphoryl donor in the phosphorylation reaction and hydrolysis of the phosphoryl group in the dephosphorylation reaction. The net result of these reactions can be viewed as the hydrolysis of ATP, which has a G of -12 kcal/mol under cellular conditions and is therefore, energetically favorable.

Residues which are the usual sites of phosphorylation are serine, threonine and tryosine hydroxyl groups. Aspartic acid, histidine and lysine can also be phosphorylated.