title: An ERK2 docking site in the Pointed domain distinguishes a subset of ETS transcription factors.
abstract: The ETS transcription factors perform distinct biological functions despite conserving a highly similar DNA-binding domain. One distinguishing property of a subset of ETS proteins is a conserved region of 80 amino acids termed the Pointed (PNT) domain. Using enzyme kinetics we determined that the Ets-1 PNT domain contains an ERK2 docking site. The docking site enhances the efficiency of phosphorylation of a mitogen-activated protein kinase (MAPK) site N-terminal to the PNT domain. The site enhances ERK2 binding rather than catalysis. Three hydrophobic residues are involved in docking, and the previously determined NMR structure indicates that these residues are clustered on the surface of the Ets-1 PNT domain. The docking site function is conserved in the PNT domain of the highly related Ets-2 but not in the ets family member GABPalpha. Ablation of the docking site in Ets-1 and Ets-2 prevented Ras pathway-mediated enhancement of the transactivation function of these proteins. This study provides structural insight into the function of a MAPK docking site and describes a unique activity for the PNT domain among a subset of ets family members.
authors.affiliation: Huntsman Cancer Institute, Department of Oncological Sciences, University of Utah, Salt Lake City, Utah 84112-5550, USA.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Seidel
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Graves
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics*; D010766:Phosphorylation; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C494042:Ets1 protein, mouse; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors; D019950:Mitogen-Activated Protein Kinase 1