A Human MAP Kinase Interactome

Mitogen Activated Protein Kinase (MAPK) pathways form the backbone of signal transduction within the mammalian cell. Here, we apply 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. A core network of 641 interactions is supported by multiple lines of evidence including conservation with yeast. Using siRNA knockdowns, we reveal that a significant number of novel interactors can modulate MAPK mediated signaling. We uncover the Na-H exchanger NHE1 as a scaffold for a novel set of MAPKs, link HSP90 chaperones to MAPK pathways, and identify MUC12 as the human analogue to the yeast signaling mucin Msb2. This study makes available a large resource of MAPK interactions along with the accompanying clone libraries. It illustrates a methodology for probing signaling networks based on functional refinement of experimentally-derived protein interaction maps.