The complexity of cell signaling and the need for a new mechanics.
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.
Hlavacek
William S
WS
Theoretical Division and Center for Nonlinear Studies, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
Faeder
James R
JR
D000818:Animals; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008954:Models, Biological; D010766:Phosphorylation; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D011956:Receptors, Cell Surface / Q000502:physiology
D011506:Proteins; D011956:Receptors, Cell Surface; D011494:Protein Kinases