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The mechanism of phosphorylation‐inducible activation of the ETS‐domain transcription factor Elk‐1
Author(s) -
Yang ShenHsi,
Shore Paul,
Willingham Nicola,
Lakey Jeremy H.,
Sharrocks Andrew D.
Publication year - 1999
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/18.20.5666
Subject(s) - phosphorylation , transcription factor , biology , phosphorylation cascade , dna binding domain , microbiology and biotechnology , allosteric regulation , dna binding protein , kinase , protein phosphorylation , biochemistry , protein kinase a , gene , receptor
Protein phosphorylation represents one of the major mechanisms for transcription factor activation. Here we demonstrate a molecular mechanism by which phosphorylation by mitogen‐activated protein (MAP) kinases leads to changes in transcription factor activity. MAP kinases stimulate DNA binding and transcriptional activation mediated by the mammalian ETS‐domain transcription factor Elk‐1. Phosphorylation of the C‐terminal transcriptional activation domain induces a conformational change in Elk‐1, which accompanies the stimulation of DNA binding. C‐terminal phosphorylation is coupled to activation of DNA binding by the N‐terminal DNA‐binding domain via an additional intermediary domain. Activation of DNA binding is mediated by an allosteric mechanism involving the key phosphoacceptor residues. Together, these results provide a molecular model for how phosphorylation induces changes in Elk‐1 activity.