Network model of survival signaling in T-cell large granular lymphocyte leukemia

The original idea of signaling pathways, as presented in the early studies of G-protein signaling (Gilman 1987; Hardman, Robison, and Sutherland 1971; Rodbell 1995) was heavily influenced by concepts of signal transduction in computer science. Each pathway was considered as an independent responding unit that coupled extracellular stimulations to specific outputs through defined signaling cascades. However, as more signaling pathways were identified, it became obvious that crosstalk was a common phenomenon among pathways, and the same pathway could participate in cellular responses against different environmental stimulations (Eungdamrong and Iyengar 2004; Ma’ayan 2008). It is now well established that molecular events in the cell occur in the context of a complex signaling network that is temporally, spatially, and concentration-wise dynamic.