April 9, 1999

Sutherland Lecture sheds light on body’s molecular switches

Sutherland Lecture sheds light on body's molecular switches


Dr. Alfred Gilman


Dr. Earl Sutherland

It was standing-room-only for the second Earl W. Sutherland Lecture.

Nobel laureate Dr. Alfred G. Gilman, Regental Professor and Chair of Pharmacology at the University of Texas Southwestern Medical Center, presented "G Proteins and Regulation of Adenylyl Cyclase."

The lecture honors Dr. Sutherland, Nobel laureate and professor of Physiology at Vanderbilt from 1963-1973. Prior to joining the Vanderbilt faculty, Dr. Sutherland was professor and chair of Pharmacology at Case Western Reserve University, where he had a profound impact on Gilman's career.

"Earl Sutherland changed my life totally," Gilman said. "He was running one of the first M.D./Ph.D. programs in the country, and he personally recruited all the members of the program. I was hooked by Earl, by cyclic AMP, and by the other students. It sealed my fate."

Gilman was awarded the 1994 Nobel Prize in Physiology or Medicine for his discovery and characterization of molecular switches called G proteins.

These proteins, so named because they bind guanosine triphosphate (GTP), are the middlemen in the process of transferring signals across the cell membrane. They switch on when signals like hormones interact with cell surface receptors. They switch off after passing the signal on to the next protein in the chain.

"This is the most common mechanism for transducing a signal across the plasma membrane," Gilman said. "Everything from sex in yeast to vision in humans depends on G proteins."

Because G proteins participate in controlling fundamental cell processes, it is no surprise that disturbances in their function can lead to disease. Faulty G proteins are the culprits in some types of cancer and hereditary endocrine disorders and may contribute to the symptoms of diabetes and alcoholism.

Gilman discussed his recent studies of other proteins that participate in the signaling chain of events. His laboratory is currently characterizing RGS proteins, members of a new family of proteins that regulate G protein signaling. RGS proteins add another level of control and complexity to signaling pathways.

Gilman also described his laboratory's efforts to understand how G proteins communicate with the enzyme adenylyl cyclase. Active adenylyl cyclase produces cyclic AMP, a so-called "second messenger," inside cells.

It was Dr. Sutherland who discovered cyclic AMP and developed the hypothesis that a hormone operates as a "first messenger" and causes the cell to produce a "second messenger" like cyclic AMP to carry the signal forward.

Dr. Sutherland was awarded the Nobel Prize in Physiology or Medicine in 1971 for his discoveries related to cellular signaling and hormone action.

"Earl Sutherland had a sixth sense about how biological systems ought to work, and all of us who worked with him held him in awe," said Joel G. Hardman, Ph.D., professor of Pharmacology, Emeritus, who joined Dr. Sutherland's laboratory in 1964 as a post-doctoral fellow.

Dr. Sutherland was a member of the National Academy of Sciences, the American Academy of Arts and Sciences, Alpha Omega Alpha, and the American Society of Biological Chemists.

In addition to the Nobel Prize, he was awarded the Banting Memorial Lectureship and Medal, the Sollman Award, the Gairdner Award, the National Medal of Science, and the Lasker Award.

The Earl W. Sutherland Lecture is sponsored by the Department of Molecular Physiology and Biophysics