title: Domains, motifs, and scaffolds: the role of modular interactions in the evolution and wiring of cell signaling circuits.
abstract: Living cells display complex signal processing behaviors, many of which are mediated by networks of proteins specialized for signal transduction. Here we focus on the question of how the remarkably diverse array of eukaryotic signaling circuits may have evolved. Many of the mechanisms that connect signaling proteins into networks are highly modular: The core catalytic activity of a signaling protein is physically and functionally separable from molecular domains or motifs that determine its linkage to both inputs and outputs. This high degree of modularity may make these systems more evolvable-in principle, novel circuits, and therefore highly innovative regulatory behaviors, can arise from relatively simple genetic events such as recombination, deletion, or insertion. In support of this hypothesis, recent studies show that such modular systems can be exploited to engineer nonnatural signaling proteins and pathways with novel behavior.
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California 94143, USA.
authors.forename: Roby P
authors.initials: RP
authors.lastname: Bhattacharyya
authors.forename: Attila
authors.initials: A
authors.lastname: Reményi
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Yeh
authors.forename: Wendell A
authors.initials: WA
authors.lastname: Lim
mesh_terms: D000818:Animals; D001665:Binding Sites; D019143:Evolution, Molecular; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D005656:Fungal Proteins; D011494:Protein Kinases