Meta-Biol

• Pathways

Both ETS1 and ETS2 contain a consensus site (PLLTP) for MAPK3 and MAPK1 (ERK1 and ERK2, respectively) in the vicinity of the pointed domain, while the pointed domain contains a docking site needed for ERK1/2 binding to ETS1/2. ETS1 and ETS2 are able to collaborate with RAS in superactivating the promoters that contain RREs (RAS response elements) that include ETS-binding sites. The cooperation of ETS1 and ETS2 with RAS activation is dependent on the phosphorylation of PLLTP threonine residue (T38 in ETS1; T72 in ETS2) (Yang et al. 1996, Seidel et al. 2002). Phosphorylation of ETS1 and ETS2 by ERK1/2 induces a conformational change that increases their affinity for the TAZ domain of the transcriptional coactivator CREBBP (CBP) and the transcriptional activation of RREs (Foulds et al. 2004, Nelson et al. 2010), although ETS1/ETS2 may interact with CREBBP in the absence of phosphorylation (Jayaraman et al. 1999). Phosphorylation of serine residue S41 of ETS1 (corresponds to serine residue S75 of ETS2) may be necessary for full activation of ETS1/2 (Nelson et al. 2010).