Format

Send to

Choose Destination
EMBO J. 2002 Dec 2;21(23):6494-504.

Recognition of ERK MAP kinase by PEA-15 reveals a common docking site within the death domain and death effector domain.

Author information

1
Laboratory of Molecular Biophysics, The Rockefeller University, New York, NY 10021, USA.

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.

PMID:
12456656
PMCID:
PMC136945
DOI:
10.1093/emboj/cdf641
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center