The Development of Phospho-specific Antibodies as Key Reagents for Identifying Signal Transduction Pathways in the Brain

A critical early contribution of Greenberg and his colleagues was the development of phosphorylation site-specific antibodies to CREB.  With these phospho-CREB specific antibodies, they were able to show that synaptic activity within the brain triggers CREB activation.  This provided the first evidence that the signal transduction pathways that had been implicated in the induction of activity-regulated genes in cell culture were also activated by neuronal activity in live animals.  Perhaps more importantly, this study was among the first to demonstrate the utility of phospho-specific antibodies for studying signal transduction pathways within cells and organisms. Subsequently, the lab has generalized the use of phospho-specific antibodies to over 50 different neuronal signaling proteins.  By making these reagents and methods available to hundreds of investigators in the field, these investigators have helped to define neural circuits that mediate a wide range of behavioral responses (e.g. sleep, feeding behavior, circadian rhythms, responses to drugs of abuse).