title: Signal transduction: From the atomic age to the post-genomic era.
abstract: We have come a long way in the 55 years since Edmond Fischer and the late Edwin Krebs discovered that the activity of glycogen phosphorylase is regulated by reversible protein phosphorylation. Many of the fundamental molecular mechanisms that operate in biological signaling have since been characterized and the vast web of interconnected pathways that make up the cellular signaling network has been mapped in considerable detail. Nonetheless, it is important to consider how fast this field is still moving and the issues at the current boundaries of our understanding. One must also appreciate what experimental strategies have allowed us to attain our present level of knowledge. We summarize here some key issues (both conceptual and methodological), raise unresolved questions, discuss potential pitfalls, and highlight areas in which our understanding is still rudimentary. We hope these wide-ranging ruminations will be useful to investigators who carry studies of signal transduction forward during the rest of the 21st century.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, California 94720-3202.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Thorner
authors.affiliation: Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037.
authors.forename: Tony
authors.initials: T
authors.lastname: Hunter
authors.affiliation: Cancer Center, Weill Cornell Medical College, New York, New York 10065.
authors.forename: Lewis C
authors.initials: LC
authors.lastname: Cantley
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724.
authors.forename: Richard
authors.initials: R
authors.lastname: Sever
mesh_terms: D019143:Evolution, Molecular; D053858:Metabolic Networks and Pathways / Q000502:physiology*; D057054:Molecular Imaging / Q000379:methods* / Q000639:trends; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping / Q000379:methods* / Q000639:trends; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*