title: Recognition of ERK MAP kinase by PEA-15 reveals a common docking site within the death domain and death effector domain.
abstract: PEA-15 is a multifunctional protein that modulates signaling pathways which control cell proliferation and cell death. In particular, PEA-15 regulates the actions of the ERK MAP kinase cascade by binding to ERK and altering its subcellular localization. The three-dimensional structure of PEA-15 has been determined using NMR spectroscopy and its interaction with ERK defined by characterization of mutants that modulate ERK function. PEA-15 is composed of an N-terminal death effector domain (DED) and a C-terminal tail of irregular structure. NMR 'footprinting' and mutagenesis identified elements of both the DED and tail that are required for ERK binding. Comparison of the DED-binding surface for ERK2 with the death domain (DD)-binding surface of Drosophila Tube revealed an unexpected similarity between the interaction modes of the DD and DED motifs in these proteins. Despite a lack of functional or sequence similarity between PEA-15 and Tube, these proteins utilize a common surface of the structurally similar DD and DED to recognize functionally diverse targets.
authors.affiliation: Laboratory of Molecular Biophysics, The Rockefeller University, New York, NY 10021, USA.
authors.forename: Justine M
authors.initials: JM
authors.lastname: Hill
authors.forename: Hema
authors.initials: H
authors.lastname: Vaidyanathan
authors.forename: Joe W
authors.initials: JW
authors.lastname: Ramos
authors.forename: Mark H
authors.initials: MH
authors.lastname: Ginsberg
authors.forename: Milton H
authors.initials: MH
authors.lastname: Werner
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001665:Binding Sites; D000939:Epitopes; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment
chemical_list: D051017:Apoptosis Regulatory Proteins; D000939:Epitopes; C490444:Pea15 protein, mouse; D010750:Phosphoproteins; D020928:Mitogen-Activated Protein Kinases