Activated AKT phosphorylates RUNX2 without affecting its association with CBFB or its nuclear localization. Based on studies using recombinant mouse Runx2, the most prominent AKT target sites in human RUNX2 are inferred to be serine residue S196 and threonine residues T198 and T200. These sites are evolutionarily conserved and match S203, T205 and T207 of the recombinant mouse Runx2 (Pande et al. 2013). In addition to phosphorylating RUNX2, which increases its affinity for some target promoters (Pande et al. 2013), AKT signaling also stabilizes RUNX2 protein. Increased AKT signaling, achieved by knocking down PTEN, a negative regulator of AKT activation, reduces RUNX2 protein degradation, which possibly involves AKT-mediated nuclear exclusion of transcription factors FOXO1 and FOXO3. Increased RUNX2 activity in response to AKT signaling is implicated in vascular calcification, a pathological feature of atherosclerosis, diabetes mellitus and renal disease (Deng et al. 2015).