How a single protein was found to link schizophrenia and depression to drugs of abuse and addiction.
By Per Svenningsson and Paul Greengard
In the early 1980s, a search for brain proteins that might be involved in communication between nerve cells turned up a 32-kilodalton protein-kinase substrate with some remarkable properties. Our group had been working under the assumption that the signaling pathways that regulate synaptic transmission might resemble the signaling pathways working elsewhere in the body, particularly the endocrine signaling involved in the breakdown of glycogen in muscle and liver.
Inspired by the work of Earl Sutherland and Edwin Krebs, who showed that cyclic AMP acting through a cyclic AMP-dependent protein kinase (PKA) facilitated this breakdown, we were tantalized by the possibility that analogous systems might be operating in the brain to produce physiological responses. John Kebabian, James Nathanson, Jy-Fan Kuo, Howard Schulman, and Mary Kennedy began looking for and ...
