Reactome | MAPKs phosphorylate ETS1 and ETS2

MAPKs phosphorylate ETS1 and ETS2

Stable Identifier

R-HSA-3132737

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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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).

Literature References

PubMed ID	Title	Journal	Year
10358095	p300/cAMP-responsive element-binding protein interactions with ets-1 and ets-2 in the transcriptional activation of the human stromelysin promoter Kurkinen, M, Dhar, R, Buttice, G, Jayaraman, G, Ferreira, E, Hauser, C, Swaminathan, S, Duggan, C, Srinivas, R, Weitzman, S, Thimmapaya, B, Williams, J, Somasundaram, K	J. Biol. Chem.	1999
15572696	Ras/mitogen-activated protein kinase signaling activates Ets-1 and Ets-2 by CBP/p300 recruitment Graves, BJ, Foulds, CE, Nelson, ML, Blaszczak, AG	Mol. Cell. Biol.	2004
20534573	Ras signaling requires dynamic properties of Ets1 for phosphorylation-enhanced binding to coactivator CBP Graves, BJ, Lee, GM, Kang, HS, Nelson, ML, Blaszczak, AG, Lau, DK, McIntosh, LP	Proc. Natl. Acad. Sci. U.S.A.	2010
8552081	Ras-mediated phosphorylation of a conserved threonine residue enhances the transactivation activities of c-Ets1 and c-Ets2 Yang, BS, Stacey, KJ, Hauser, CA, Hume, DA, Ostrowski, MC, Van Beveren, C, Maki, RA, Henkel, G, Colman, MS	Mol. Cell. Biol.	1996
11782450	An ERK2 docking site in the Pointed domain distinguishes a subset of ETS transcription factors Graves, BJ, Seidel, JJ	Genes Dev.	2002