Signaling netwErks get the global treatment 英文参考文献.docVIP

Minireview Signaling netwErks get the global treatment Michael B Yaffe*?? and Forest M White*? Addresses: *Center for Cancer Research, ?Department of Biology and ?Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Correspondence: Michael B Yaffe. Email: myaffe@ Published: 1 February 2007 Genome Biology 2007, 8:202 (doi:10.1186/gb-2007-8-1-202) The electronic version of this article is the complete one and can be found online at /2007/8/1/202 ? 2007 BioMed Central Ltd Abstract Two landmark studies of cell signaling, by RNA interference and phosphoproteomics, provide complementary global views of the pathways downstream of receptor kinases, including those regulated by Erks. In the prelapsarian days of signal transduction, pathways were simple, everything was linear, and life was good. Like the misfortunes that befell Voltaire’s Candide, however, the unfortunate intervention of reality has clouded that wonder- fully innocent view by adding layer upon layer of complexity to what was once neat, clean and relatively easy to think about. (RNAi) screening to functionally annotate proteins regula- ting activation of extracellular signal-regulated kinases (ERKs), whereas Olsen et al. [2] carried out a proteome- wide quantitative analysis of protein-phosphorylation dynamics in the epidermal growth factor receptor (EGFR) signaling network. Although neither method by itself provides all the data necessary to understand the signaling networks, together, they reveal, like peeling the layers from an onion, many potential molecular mechanisms that underlie complex biological processes. Consider the signaling pathways that regulate protein phos- phorylation, the most common post-translational modifica- tion of proteins. These pathways and networks regulate almost all aspects of cell biology and, when dysregulat