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A human MAP kinase interactome.

Mitogen-activated protein kinase (MAPK) pathways form the backbone of signal transduction in the mammalian cell. Here we applied a systematic experimental and computational approach to map 2,269 interactions between human MAPK-related proteins and other cellular machinery and to assemble these data into functional modules. Multiple lines of evidence including conservation with yeast supported a core network of 641 interactions. Using small interfering RNA knockdowns, we observed that approximately one-third of MAPK-interacting proteins modulated MAPK-mediated signaling. We uncovered the Na-H exchanger NHE1 as a potential MAPK scaffold, found links between HSP90 chaperones and MAPK pathways and identified MUC12 as the human analog to the yeast signaling mucin Msb2. This study makes available a large resource of MAPK interactions and clone libraries, and it illustrates a methodology for probing signaling networks based on functional refinement of experimentally derived protein-interaction maps.

Pubmed ID: 20936779

Authors

  • Bandyopadhyay S
  • Chiang CY
  • Srivastava J
  • Gersten M
  • White S
  • Bell R
  • Kurschner C
  • Martin C
  • Smoot M
  • Sahasrabudhe S
  • Barber DL
  • Chanda SK
  • Ideker T

Journal

Nature methods

Publication Data

October 8, 2010

Associated Grants

  • Agency: NIMH NIH HHS, Id: P30 MH062261
  • Agency: NIMH NIH HHS, Id: P30 MH062261-05
  • Agency: NIMH NIH HHS, Id: P30 MH062261-05S1
  • Agency: NIMH NIH HHS, Id: P30 MH062261-06A1
  • Agency: NIMH NIH HHS, Id: P30 MH062261-07
  • Agency: NIMH NIH HHS, Id: P30 MH062261-08
  • Agency: NIMH NIH HHS, Id: P30 MH062261-09
  • Agency: NIMH NIH HHS, Id: P30 MH062261-10
  • Agency: NIMH NIH HHS, Id: P30-MH062261
  • Agency: NIGMS NIH HHS, Id: P50 GM085764
  • Agency: NIGMS NIH HHS, Id: R01 GM070743
  • Agency: NIGMS NIH HHS, Id: R01 GM070743-01
  • Agency: NIGMS NIH HHS, Id: R01 GM070743-02
  • Agency: NIGMS NIH HHS, Id: R01 GM070743-03
  • Agency: NIGMS NIH HHS, Id: R01 GM070743-03S1
  • Agency: NIGMS NIH HHS, Id: R01 GM070743-04
  • Agency: NIGMS NIH HHS, Id: R01 GM070743-05
  • Agency: NIGMS NIH HHS, Id: R01 GM070743-06
  • Agency: NIGMS NIH HHS, Id: R01 GM070743-07
  • Agency: NIGMS NIH HHS, Id: R01 GM070743-08
  • Agency: NIGMS NIH HHS, Id: R01-GM070743
  • Agency: NIGMS NIH HHS, Id: R01-GM47413

Mesh Terms

  • Base Sequence
  • Cation Transport Proteins
  • Cell Line
  • Cell Membrane
  • Cloning, Molecular
  • DNA, Complementary
  • HSP90 Heat-Shock Proteins
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Luciferases
  • MAP Kinase Signaling System
  • Mitogen-Activated Protein Kinases
  • Molecular Sequence Data
  • Mucins
  • NF-kappa B
  • Proteomics
  • RNA, Small Interfering
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Sodium-Hydrogen Antiporter
  • Transcription Factor AP-1
  • Two-Hybrid System Techniques