Title: A Human Map Kinase Interactome

Authors: Sourav Bandyopadhyay, Chih-yuan Chiang, Jyoti Srivastava, Merril Gersten, Suhaila White, Russell Bell, Cornelia Kurschner,Christopher H Martin, Mike Smoot, Sudhir Sahasrabudhe, Diane L Barber, Sumit K Chanda & Trey Ideker

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 a large fraction of previously unidentified interactors modulated MAPK-mediated signaling. We uncovered the Na-H exchanger NHE1 as a potential MAPK scaffold, suggest 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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