Alfred Gilman

G-proteins are intracellular signaling proteins that act as molecular switches, cycling between an active GTP-bound state and an inactive GDP-bound state. Gilman discovered them while studying how hormone receptors on the cell surface communicate with intracellular enzymes like adenylate cyclase, the enzyme that produces cyclic AMP. His lab at the University of Texas Southwestern identified and purified the Gs and Gi proteins that stimulate and inhibit adenylate cyclase, respectively.

Gilman shared the 1994 Nobel Prize in Physiology or Medicine with Martin Rodbell of the National Institute of Environmental Health Sciences. Rodbell had earlier introduced the concept of transducers—the G-proteins—that serve as intermediaries between receptors and intracellular effectors, coining the term signal transduction. Gilman built on Rodbell's framework by biochemically isolating and characterizing the actual G-protein molecules.

Gilman spent most of his career at the University of Texas Southwestern Medical Center in Dallas, where he joined the faculty in 1981. He worked in the same department that produced several other Nobel laureates in signal transduction, including Michael Brown and Joseph Goldstein, who won in 1985 for their LDL receptor work. Gilman later served as dean of Southwestern Medical School and chief scientific officer of the Cancer Prevention and Research Institute of Texas (CPRIT).

The human genome encodes dozens of different G-protein alpha subunits that regulate a wide array of cellular functions, from vision (transducin in retinal rods) to smell (Golf in olfactory neurons) to heart rate regulation. G-protein-coupled receptors (GPCRs), which activate G-proteins, are the largest family of cell-surface receptors and are targets for an estimated one-third of all FDA-approved drugs. Gilman's foundational work on Gs and Gi opened the door to this entire field of drug development.