期刊
NATURE METHODS
卷 7, 期 10, 页码 801-U50出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/NMETH.1506
关键词
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资金
- US National Institutes of Health [R01-GM070743, R01-GM47413, P30-MH062261]
- Unilever PLC
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM047413, P50GM085764, R01GM070743] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF MENTAL HEALTH [P30MH062261] Funding Source: NIH RePORTER
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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