The human phosphotyrosine signaling network: Evolution and hotspots of hijacking in cancer

• DOI: 10.1101/gr.128819.111
• Publication Date: 2011-12-23T05:48:10Z
• Authors: Lei Li; Chabane Tibiche; Cong Fu; Tomonori Kaneko; Michael F. Moran; Martin R. Schiller; Shawn Shun-Cheng Li; Edwin Wang
• Keywords: Cell Signaling

Phosphotyrosine (pTyr) signaling, which plays a central role in cell-cell and cell-environment interactions, has been considered to be an evolutionary innovation multicellular metazoans. However, neither the emergence nor evolution of human pTyr signaling system is currently understood. Tyrosine kinase (TK) circuits, each consists TK writer, substrate, related reader, such as Src homology (SH) 2 domains pTyr-binding (PTB) domains, comprise core machinery network. In this study, we analyzed trajectories 583 literature-derived 50,000 computationally predicted circuits 19 representative eukaryotic species assigned their origins. We found that for intracellular originated largely from primitive organisms, whereas inter- or extracellular experienced significant expansion bilaterian lineage through "back-wiring" newly evolved kinases substrates SH2/PTB domains. Conversely, are involved tissue-specific mainly vertebrates by back-wiring vertebrate Importantly, cancer preferentially employs sites, linked more circuits. Our work provides insights into paths suggests use network approach intervention targeting key sites associated hubs