Specificity in signal transduction: from phosphotyrosine-SH2 domain interactions to complex cellular systems.
Over the last two decades, a new and unifying concept of cellular organization has emerged in which modular protein-protein interactions provide an underlying framework through which signaling pathways are assembled and controlled. In this scheme, posttranslational modifications such as phosphorylation commonly exert their biological effects by regulating molecular interactions, exemplified by the ability of phosphotyrosine sites to bind selectively to SH2 domains. Although these interactions are rather simple in isolation, they can nonetheless be exploited to generate complex cellular systems. Here, I discuss experiments that have led to this view of dynamic cellular behavior and identify some current and future areas of interest in cell signaling.
Pawson
Tony
T
Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada. pawson@mshri.on.ca
D000818:Animals; D005656:Fungal Proteins / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000737:chemistry*; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D018909:src Homology Domains
D005656:Fungal Proteins; D019000:Phosphotyrosine