RUNX2 is phosphorylated by activated ERKs (MAPK3 and MAPK1) on at least two conserved serine residues. ERK-mediated phosphorylation is not known to affect binding of RUNX2 to CBFB and is therefore shown to happen in the context of the RUNX2:CBFB complex. RUNX2 phosphorylated by ERKs shows enhanced binding to RUNX2 response elements in the osteocalcin (BGLAP) gene promoter, resulting in increased BGLAP gene transcription (Ge et al. 2009).
ERK-mediated phosphorylation of RUNX2 in response to FGF2 signaling is thought to promote RUNX2 isomerization by PIN1 prolyl isomerase, which facilitates EP300 (p300) mediated acetylation and stabilization of RUNX2 (Yoon et al. 2014).