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A human MAP kinase interactome.

Nature methods | Oct 8, 2010

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 RIS Download

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

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Associated grants

  • Agency: NIMH NIH HHS, Id: P30 MH062261-06A1
  • Agency: NIMH NIH HHS, Id: P30 MH062261-07
  • Agency: NIGMS NIH HHS, Id: R01 GM070743-03
  • Agency: NIMH NIH HHS, Id: P30 MH062261
  • Agency: NIGMS NIH HHS, Id: R01 GM070743-08
  • Agency: NIGMS NIH HHS, Id: R01 GM070743-04
  • Agency: NIGMS NIH HHS, Id: R01-GM070743
  • Agency: NIGMS NIH HHS, Id: R01 GM070743-03S1
  • Agency: NIMH NIH HHS, Id: P30 MH062261-05S1
  • Agency: NIGMS NIH HHS, Id: R01 GM047413
  • Agency: NIGMS NIH HHS, Id: R01 GM070743-05
  • Agency: NIMH NIH HHS, Id: P30-MH062261
  • Agency: NIGMS NIH HHS, Id: R01 GM070743-07
  • Agency: NIGMS NIH HHS, Id: R01-GM47413
  • Agency: NIMH NIH HHS, Id: P30 MH062261-08
  • Agency: NIMH NIH HHS, Id: P30 MH062261-05
  • Agency: NIGMS NIH HHS, Id: R01 GM070743-02
  • Agency: NIGMS NIH HHS, Id: P50 GM085764
  • Agency: NIGMS NIH HHS, Id: R01 GM070743-06
  • Agency: NIGMS NIH HHS, Id: R01 GM070743-01
  • Agency: NIGMS NIH HHS, Id: R01 GM070743
  • Agency: NIMH NIH HHS, Id: P30 MH062261-09
  • Agency: NIMH NIH HHS, Id: P30 MH062261-10

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