<p>Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyse the reverse process. Protein kinases fall into three broad classes, characterised with respect to substrate specificity [<cite idref="PUB00005115"/>]:</p><p> <ul> <li>Serine/threonine-protein kinases</li><li>Tyrosine-protein kinases</li><li>Dual specific protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins)</li> </ul> </p><p>Protein kinase function has been evolutionarily conserved from <taxon tax_id="562">Escherichia coli</taxon> to human [<cite idref="PUB00020114"/>]. Protein kinases play a role in a multitude of cellular processes, including division, proliferation, apoptosis, and differentiation [<cite idref="PUB00015362"/>]. Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins. The catalytic subunits of protein kinases are highly conserved, and several structures have been solved [<cite idref="PUB00034898"/>], leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases [<cite idref="PUB00034899"/>].</p><p>This group of proteins is comprised entirely of phosphatidylinositol 3- and phosphatidylinositol 4-kinases. Phosphatidylinositol 3-kinase (PI3-kinase) [<cite idref="PUB00000875"/>] is an enzyme that phosphorylates phosphoinositides on the 3-hydroxyl group of the inositol ring. The three products of PI3-kinase, PI-3-P, PI-3,4-P(2) and PI-3,4,5-P(3), function as secondary messengers in cell signalling. Phosphatidylinositol 4-kinase (PI4-kinase) [<cite idref="PUB00001254"/>] acts on phosphatidylinositol (PI) in the first committed step of the production of the secondary messenger inositol-1,4,5-trisphosphate. The PI3- and PI4-kinases share a well-conserved domain at their C-terminal section, which is distantly related to the catalytic domain of protein kinases [<cite idref="PUB00000893"/>, <cite idref="PUB00007087"/>]. The catalytic domain of PI3K has a bilobal structure with a small N-terminal lobe and a large C-terminal lobe; this structure is often found in other ATP-dependent kinases. The core of this catalytic domain is the most conserved region of the PI3Ks. The ATP cofactor binds in the crevice formed by the N-and C-terminal lobes, a loop between two strands provides a hydrophobic pocket for binding of the adenine moiety, and a lysine residue interacts with the alpha-phosphate. In contrast to other protein kinases, the PI3K loop interacts with the phosphates of the ATP, known as the glycine-rich or P-loop, contains no glycine residues. Instead, contact with the ATP -phosphate is maintained through the side chain of a conserved serine residue.</p> <p>Synonym(s): PIK</p>