RAC serine/threonine-protein kinases (AKT, PKB) are serine/threonine kinases belonging to the cAMP-dependent protein kinase A/ protein kinase G/ protein kinase C (AGC) superfamily of protein kinases. They share structural homology within their catalytic domains and have similar mechanisms of activation. Mammals have three AKT genes, named RAC-alpha serine/threonine-protein kinase (AKT1, PKB, PKB-alpha), RAC-beta serine/threonine-protein kinase (AKT2, PKB-beta and RAC-gamma serine/threonine-protein kinase (AKT3, PKB-gamma, STK2). All share a conserved domain structure: an amino terminal pleckstrin homology (PH) domain, a central kinase domain and a carboxyl-terminal regulatory domain that contains a hydrophobic motif that is characteristic of AGC kinases. The PH domain interacts with membrane lipid products such as phosphatidylinositol (3,4,5) trisphosphate (PIP3) produced by phosphatidylinositol 3-kinase (PI3-kinase). Biochemical analysis. The PH domain of AKT binds to PIP3 and PIP2 with similar affinity (James et al. 1996, Frech et al. 1997). The kinase catalytic domain of Akt/PKB is highly similar to other AGC kinases (Peterson & Schreiber 1999). Phosphorylation of a conserved threonine residue in this region (T308 in AKT1) results in partial activation (Alessi et al. 1996). The carboxyl terminal extension has the hydrophobic motif FPQFSY. Phosphorylation of serine or threonine residue in this motif is necessary for full kinase activation. Deletion of this motif completely abolishes activity (Andjelkovi? et al. 1997).