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Sci. Signal., 28 July 2009
Vol. 2, Issue 81, p. pe46
The Complexity of Cell Signaling and the Need for a New Mechanics
William S. Hlavacek1,2 and
James R. Faeder3*
1 Theoretical Division and Center for Nonlinear Studies, Los Alamos National Laboratory, Los Alamos, NM 87545, USA. 2 Department of Biology, University of New Mexico, Albuquerque, NM 87131, USA. 3 Department of Computational Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA.
Cell signaling systems respond to multiple inputs, such as ligands of cell-surface receptors; and produce multiple outputs, such as changes in gene expression and cellular activities, including motility, proliferation, and death. This "macroscopic" input-output behavior is generated by a web of molecular interactions that can be viewed as taking place at a lower, "microscopic" level. These interactions prominently involve posttranslational modification of proteins and the nucleation of protein complexes. Behaviors at both the micro- and macroscopic levels are complex and must be probed systematically and characterized quantitatively as a prelude to the development of a predictive understanding of a cell signaling system. We must also have a theoretical framework or a mechanics within which we can determine how macroscopic behaviors emerge from known microscopic behaviors or change with manipulations of microscopic behaviors. To connect behaviors at both levels, we suggest that a new mechanics is now required. Newly available data support the idea that this mechanics should enable one to track the site-specific details of molecular interactions in a model, such as the phosphorylation status of individual amino acid residues within a protein.
Robert C. Hsueh, Madhusudan Natarajan, Iain Fraser, Blake Pond, Jamie Liu, Susanne Mumby, Heping Han, Lily I. Jiang, Melvin I. Simon, Ronald Taussig, and Paul C. Sternweis (19 May 2009) Sci. Signal.2 (71), ra22.
[DOI: 10.1126/scisignal.2000054] |Editor's Summary »|Abstract »|Full Text »|PDF »