Specialized domains that mediate specific interactions are present in many signaling proteins. The “wiring” of many signal-transduction pathways is based on particular protein domains that mediate the interactions between protein components of a particular signaling cascade. We have encountered several of them, including pleckstrin homology domains, which facilitate protein interactions with the lipid PIP3; SH2 domains, which mediate interactions with polypeptides containing phosphorylated tyrosine residues; and SH3 domains, which interact with peptide sequences that contain multiple proline residues. Many other such domain families exist. In many cases, individual members of each domain family have unique features that allow them to bind to their targets only within a particular sequence context, making them specific for a given signaling pathway and avoiding unwanted cross-talk. Signal-transduction pathways have evolved in large part by the incorporation of DNA fragments encoding these domains into genes encoding pathway components.
The presence of these domains is tremendously helpful to scientists trying to unravel signal-transduction pathways. When a protein in a signal-transduction pathway is identified, its amino acid sequence can be analyzed for the presence of these specialized domains by the methods described in Chapter 6. If one or more domains of known function is found, it is often possible to develop clear hypotheses about potential binding partners and signal-transduction mechanisms.