Alfred G. Gilman

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For the co-author of The Pharmacological Basis of Therapeutics, see Alfred Gilman, Sr.. For the Episcopal bishop, see Alfred Gilman (bishop).
Alfred G. Gilman
Born Alfred Goodman Gilman
July 1, 1941
New Haven, Connecticut
Nationality American
Fields pharmacologist
Alma mater Case Western Reserve University (MD-Ph.D., 1969)
Known for G-proteins
Notable awards John J. Abel Award (1975)
Richard Lounsbery Award (1987)
Nobel Prize in Physiology or Medicine (1994)
Spouse Kathryn Hedlund (3 children)

Alfred Goodman Gilman (born July 1, 1941) is an American pharmacologist and biochemist. He shared the 1994 Nobel Prize in Physiology or Medicine with Martin Rodbell for their discoveries regarding G-proteins.

G-proteins are a vital intermediary between the extracellular activation of receptors (GPCR) on the cell membrane and actions within the cell. Rodbell had shown in the 1960s that GTP was involved in cell signaling. It was Gilman who actually discovered the proteins that interacted with the GTP to initiate signalling cascades within the cell.

Family history[edit]

Gilman was born in New Haven, Connecticut. His parents were Mabel (Schmidt) and Alfred Gilman, a professor at Yale University and one of the authors of the classic pharmacology textbook The Pharmacological Basis of Therapeutics; he chose his son's middle name in honor of his co-author Louis S. Goodman. Alfred Goodman Gilman was contributing editor of the tenth (2001) edition of the textbook.[1]

Education[edit]

Gilman graduated from Yale with his B.S. in 1962. He then entered a combined MD/PhD program at Case Western Reserve University School of Medicine in Cleveland, Ohio where he wanted to study under Nobel laureate pharmacologist Earl Sutherland. Sutherland was departing for Vanderbilt University, so Gilman studied under Sutherland's young collaborator, Theodore Rall. Gilman graduated from Case Western in 1969, then did his post-doctoral studies at the National Institutes of Health with Nobel laurate Marshall Nirenberg from 1969 until 1971.

Professional History[edit]

In 1971, Gilman became a professor of pharmacology at the University of Virginia, School of Medicine, in Charlottesville, Virginia. In 1981, he became chairman of the Department of Pharmacology at the University of Texas Southwestern Medical Center at Dallas. He was elected as a member of the National Academy of Sciences in 1986. In addition to winning the Nobel Prize in 1994, he won the Albert Lasker Award for Basic Medical Research as well as the Louisa Gross Horwitz Prize from Columbia University in 1989 together with Edwin Krebs. In 2005, he was elected as Dean of University of Texas Southwestern Medical School in Dallas, Texas. He also serves on the board of advisors of Scientists and Engineers for America, an organization focused on promoting sound science in American government.

Key papers[edit]

Norepinephrine stimulated increase of cyclic AMP levels in developing mouse brain cell cultures. Science. 1971 October 15;174(6):292. PMID 4330303.

Regulation of adenosine 3',5'-cyclic monophosphate metabolism in cultured neuroblastoma cells. Nature. 1971 December 10;234(5328):356-8. PMID 4332686.

Fluorescent modification of adenosine 3',5'-monophosphate: spectroscopic properties and activity in enzyme systems. Science. 1972 July 21;177(45):279-80. PMID 4339302.

The regulatory component of adenylate cyclase. Purification and properties. J Biol Chem. 1981 November 25;256(22):11517-26. PMID 6271754.

The regulatory component of adenylate cyclase. Purification and properties of the turkey erythrocyte protein. J Biol Chem. 1981 December 25;256(24):12911-9. PMID 6273414.

Requirements for cholera toxin-dependent ADP-ribosylation of the purified regulatory component of adenylate cyclase. J Biol Chem. 1982 January 10;257(1):20-3. PMID 6273425.

The guanine nucleotide activating site of the regulatory component of adenylate cyclase. Identification by ligand binding. J Biol Chem. 1982 October 10;257(19):11416-23. PMID 6288684.

The regulatory components of adenylate cyclase and transducin. A family of structurally homologous guanine nucleotide-binding proteins. J Biol Chem. 1983 June 10;258(11):7059-63. PMID 6304074.

The subunits of the stimulatory regulatory component of adenylate cyclase. Resolution, activity, and properties of the 35,000-dalton (beta) subunit. J Biol Chem. 1983 September 25;258(18):11361-8. PMID 6309843.

The subunits of the stimulatory regulatory component of adenylate cyclase. Resolution of the activated 45,000-dalton (alpha) subunit. J Biol Chem. 1983 September 25;258(18):11369-76. PMID 6309844.

Homologies between signal transducing G proteins and ras gene products. Science. 1984 November 16;226(4676):860-2. PMID 6436980.

G proteins and dual control of adenylate cyclase. Cell. 1984 Mar;36(3):577-9. PMID 6321035.

Inhibition of receptor-mediated release of arachidonic acid by pertussis toxin. Cell. 1984 Dec;39(2 Pt 1):301-8. PMID 6094010.

Molecular cloning of complementary DNA for the alpha subunit of the G protein that stimulates adenylate cyclase. Science. 1985 September 20;229(4719):1274-7. PMID 3839937.

Splice variants of the alpha subunit of the G protein Gs activate both adenylyl cyclase and calcium channels. Science. 1989 February 10;243(4892):804-7. PMID 2536957.

Adenylyl cyclase amino acid sequence: possible channel- or transporter-like structure. Science. 1989 June 30;244(4912):1558-64. PMID 2472670.

Type-specific regulation of adenylyl cyclase by G protein beta gamma subunits. Science. 1991 December 6;254(5037):1500-3. PMID 1962211.

Inhibition of adenylyl cyclase by Gi alpha. Science. 1993 July 9;261(5118):218-21. PMID 8327893.

Recombinant G-protein beta gamma-subunits activate the muscarinic-gated atrial potassium channel. Nature. 1994 March 17;368(6468):255-7. PMID 8145826.

Structures of active conformations of Gi alpha 1 and the mechanism of GTP hydrolysis. Science. 1994 September 2;265(5177):1405-12. doi:10.1126/science.8073283 PMID 8073283.

Construction of a soluble adenylyl cyclase activated by Gs alpha and forskolin. Science. 1995 June 23;268(5218):1769-72. PMID 7792604.

Tertiary and quaternary structural changes in Gi alpha 1 induced by GTP hydrolysis. Science. 1995 November 10;270(5238):954-60. PMID 7481799.

The structure of the G protein heterotrimer Gi alpha 1 beta 1 gamma 2. Cell. 1995 December 15;83(6):1047-58. PMID 8521505.

GAIP and RGS4 are GTPase-activating proteins for the Gi subfamily of G protein alpha subunits. Cell. 1996 August 9;86(3):445-52. doi:10.1016/S0092-8674(00)80117-8 PMID 8756726.

Crystal structure of the adenylyl cyclase activator Gsalpha. Science. 1997 December 12;278(5345):1943-7. PMID 9395396.

Crystal structure of the catalytic domains of adenylyl cyclase in a complex with Gsalpha.GTPgammaS. Science. 1997 December 12;278(5345):1907-16. PMID 9417641.

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