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A human MAP kinase interactome

Nature Methods volume 7, pages 801–805 (2010)Cite this article

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Abstract

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.

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Figure 1: Functional properties of the MAPK network.
Figure 2: Protein subnetworks reveal known and putative MAPK scaffolds.
Figure 3: Functional modules in the core network.

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Acknowledgements

We thank R. Kelley, S. Suthram and G. Warner for assistance on various aspects of this work. This work was supported by the US National Institutes of Health (R01-GM070743, R01-GM47413 and P30-MH062261) and Unilever PLC.

Author information

Author notes

  1. Sumit K Chanda

    Present address: Present address: Infectious and Inflammatory Disease Center, Sanford-Burnham Institute for Medical Research, La Jolla, California, USA.,

Authors and Affiliations

  1. Departments of Medicine and Bioengineering, University of California at San Diego, La Jolla, California, USA

    Sourav Bandyopadhyay, Merril Gersten, Mike Smoot & Trey Ideker

  2. Program in Bioinformatics, University of California at San Diego, La Jolla, California, USA

    Sourav Bandyopadhyay, Merril Gersten & Trey Ideker

  3. The Genomics Institute of the Novartis Research Foundation, San Diego, California, USA

    Chih-yuan Chiang, Suhaila White & Sumit K Chanda

  4. Department of Cell and Tissue Biology, University of California at San Francisco, San Francisco, California, USA

    Jyoti Srivastava & Diane L Barber

  5. Prolexys Pharmaceuticals, Inc., Salt Lake City, Utah, USA

    Russell Bell, Cornelia Kurschner, Christopher H Martin & Sudhir Sahasrabudhe

  6. Institute for Genomic Medicine, University of California at San Diego, La Jolla, California, USA

    Trey Ideker

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Contributions

S.B., R.B., S.S. and T.I. conceived the study; C.-y.C., J.S., S.W., R.B., C.K. and C.H.M. performed the experiments; S.B., M.G. and M.S. analyzed the data; S.B., T.I., S.S., D.L.B. and S.K.C. wrote the paper and guided the study.

Corresponding authors

Correspondence to Sudhir Sahasrabudhe or Trey Ideker.

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Competing interests

R.B. is a shareholder of Prolexys Pharmaceuticals, Inc. S.S. is an employee, scientific founder and shareholder of Prolexys Pharmaceuticals Inc.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–3 and Supplementary Tables 3,5,7 (PDF 534 kb)

Supplementary Table 1

List of binary Y2H interactions including annotations. (XLS 457 kb)

Supplementary Table 2

Core high-confidence MAPK Y2H interactions. (XLS 96 kb)

Supplementary Table 4

List of 134 triplets containing two or more interactions from the core MAPK Y2H network. (XLS 42 kb)

Supplementary Table 6

List of human protein-protein interactions used as a reference set and for module finding. (XLS 1784 kb)

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Bandyopadhyay, S., Chiang, Cy., Srivastava, J. et al. A human MAP kinase interactome. Nat Methods 7, 801–805 (2010). https://doi.org/10.1038/nmeth.1506

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