Alfred G. Gilman
Encyclopedia
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.
. His father, Alfred Gilman
, was 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.
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.
, 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.
Regulation of adenosine 3',5'-cyclic monophosphate metabolism in cultured neuroblastoma cells. Nature. 1971 Dec 10;234(5328):356-8. PMID 4332686.
Fluorescent modification of adenosine 3',5'-monophosphate: spectroscopic properties and activity in enzyme systems. Science. 1972 Jul 21;177(45):279-80. PMID 4339302.
The regulatory component of adenylate cyclase. Purification and properties. J Biol Chem. 1981 Nov 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 Dec 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 Jan 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 Oct 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 Jun 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 Sep 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 Sep 25;258(18):11369-76. PMID 6309844.
Homologies between signal transducing G proteins and ras gene products. Science. 1984 Nov 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 Sep 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 Feb 10;243(4892):804-7. PMID 2536957.
Adenylyl cyclase amino acid sequence: possible channel- or transporter-like structure. Science. 1989 Jun 30;244(4912):1558-64. PMID 2472670.
Type-specific regulation of adenylyl cyclase by G protein beta gamma subunits. Science. 1991 Dec 6;254(5037):1500-3. PMID 1962211.
Inhibition of adenylyl cyclase by Gi alpha. Science. 1993 Jul 9;261(5118):218-21. PMID 8327893.
Recombinant G-protein beta gamma-subunits activate the muscarinic-gated atrial potassium channel. Nature. 1994 Mar 17;368(6468):255-7. PMID 8145826.
Structures of active conformations of Gi alpha 1 and the mechanism of GTP hydrolysis. Science. 1994 Sep 2;265(5177):1405-12. PMID 8073283.
Construction of a soluble adenylyl cyclase activated by Gs alpha and forskolin. Science. 1995 Jun 23;268(5218):1769-72. PMID 7792604.
Tertiary and quaternary structural changes in Gi alpha 1 induced by GTP hydrolysis. Science. 1995 Nov 10;270(5238):954-60. PMID 7481799.
The structure of the G protein heterotrimer Gi alpha 1 beta 1 gamma 2. Cell. 1995 Dec 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 Aug 9;86(3):445-52. PMID 8756726.
Crystal structure of the adenylyl cyclase activator Gsalpha. Science. 1997 Dec 12;278(5345):1943-7. PMID 9395396.
Crystal structure of the catalytic domains of adenylyl cyclase in a complex with Gsalpha.GTPgammaS. Science. 1997 Dec 12;278(5345):1907-16. PMID 9417641.
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
pharmacologist
Pharmacology
Pharmacology is the branch of medicine and biology concerned with the study of drug action. More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function...
and biochemist
Biochemistry
Biochemistry, sometimes called biological chemistry, is the study of chemical processes in living organisms, including, but not limited to, living matter. Biochemistry governs all living organisms and living processes...
. He shared the 1994 Nobel Prize in Physiology or Medicine
Nobel Prize in Physiology or Medicine
The Nobel Prize in Physiology or Medicine administered by the Nobel Foundation, is awarded once a year for outstanding discoveries in the field of life science and medicine. It is one of five Nobel Prizes established in 1895 by Swedish chemist Alfred Nobel, the inventor of dynamite, in his will...
with Martin Rodbell
Martin Rodbell
Martin Rodbell was an American biochemist and molecular endocrinologist who is best known for his discovery of G-proteins. He shared the 1994 Nobel Prize in Physiology or Medicine with Alfred G...
for their discoveries regarding G-proteins.
G-proteins are a vital intermediary between the extracellular activation of receptors (GPCR
G protein-coupled receptor
G protein-coupled receptors , also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors , comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal...
) on the cell membrane and actions within the cell. Rodbell had shown in the 1960s that GTP
Guanosine triphosphate
Guanosine-5'-triphosphate is a purine nucleoside triphosphate. It can act as a substrate for the synthesis of RNA during the transcription process...
was involved in cell signaling. It was Gilman who actually discovered the proteins that interacted with the GTP to initiate signalling cascades
Signal transduction
Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...
within the cell.
Family history
Gilman was born in New Haven, ConnecticutNew Haven, Connecticut
New Haven is the second-largest city in Connecticut and the sixth-largest in New England. According to the 2010 Census, New Haven's population increased by 5.0% between 2000 and 2010, a rate higher than that of the State of Connecticut, and higher than that of the state's five largest cities, and...
. His father, Alfred Gilman
Alfred Gilman (sr.)
See also Alfred G. Gilman.Alfred Gilman was an Americanpharmacologistat Yale University, School of Medicine, later, at Columbia College of Physicians and Surgeons and Albert Einstein College of Medicine. He published the classic textbook The Pharmacological Basis of Therapeutics with his...
, was a professor at Yale University
Yale University
Yale University is a private, Ivy League university located in New Haven, Connecticut, United States. Founded in 1701 in the Colony of Connecticut, the university is the third-oldest institution of higher education in the United States...
and one of the authors of the classic pharmacology textbook The Pharmacological Basis of Therapeutics
Goodman & Gilman's The Pharmacological Basis of Therapeutics
thumb|right|[[Alfred Gilman, Sr.|Alfred Gilman]].thumb|right|Louis S. Goodman.Goodman & Gilman's The Pharmacological Basis of Therapeutics is an American textbook of pharmacology. First published in 1941, the book is in its twelfth edition , and has the reputation of being the "bible of pharmacology"...
; 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.
Education
Gilman graduated from Yale with his B.S.Bachelor of Science
A Bachelor of Science is an undergraduate academic degree awarded for completed courses that generally last three to five years .-Australia:In Australia, the BSc is a 3 year degree, offered from 1st year on...
in 1962. He then entered a combined MD/PhD
MD/PhD
MD/PhD refers to an education which includes both the medical training of a physician with the rigor of a scientific researcher . It can refer to the designation given to a person who has graduated from such an education, or an educational program which incorporates both curricula.-Profession:An...
program at Case Western Reserve University School of Medicine
Case Western Reserve University School of Medicine
Case Western Reserve School of Medicine is one of the graduate schools of Case Western Reserve University, and is located in the University Circle neighborhood of Cleveland, Ohio. The School of Medicine is among the top 25 medical schools in America and is the top-ranked medical school of Ohio in...
in Cleveland, Ohio where he wanted to study under Nobel laureate pharmacologist Earl Sutherland. Sutherland was departing for Vanderbilt University
Vanderbilt University
Vanderbilt University is a private research university located in Nashville, Tennessee, United States. Founded in 1873, the university is named for shipping and rail magnate "Commodore" Cornelius Vanderbilt, who provided Vanderbilt its initial $1 million endowment despite having never been to the...
, 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
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
with Nobel laurate Marshall Nirenberg from 1969 until 1971.
Professional History
In 1971 Gilman became a professor of pharmacology at the University of VirginiaUniversity of Virginia
The University of Virginia is a public research university located in Charlottesville, Virginia, United States, founded by Thomas Jefferson...
, 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
University of Texas Southwestern Medical Center at Dallas
The University of Texas Southwestern Medical Center is one of the biomedical research institutions of the University of Texas System, incorporating three degree-granting institutions, four affiliated hospitals, including Parkland Memorial, the teaching hospital, and biomedical research...
. He was elected as a member of the National Academy of Sciences
United States National Academy of Sciences
The National Academy of Sciences is a corporation in the United States whose members serve pro bono as "advisers to the nation on science, engineering, and medicine." As a national academy, new members of the organization are elected annually by current members, based on their distinguished and...
in 1986. In addition to winning the Nobel Prize in 1994, he won the Albert Lasker Award for Basic Medical Research
Albert Lasker Award for Basic Medical Research
The Albert Lasker Award for Basic Medical Research is one of the prizes awarded by the Lasker Foundation for the understanding, diagnosis, prevention, treatment, and cure of disease...
as well as the Louisa Gross Horwitz Prize
Louisa Gross Horwitz Prize
Louisa Gross Horwitz Prize for Biology or Biochemistry is an annual prize awarded by Columbia University to a researcher or group of researchers that have made an outstanding contribution in basic research in the fields of biology or biochemistry....
from Columbia University
Columbia University
Columbia University in the City of New York is a private, Ivy League university in Manhattan, New York City. Columbia is the oldest institution of higher learning in the state of New York, the fifth oldest in the United States, and one of the country's nine Colonial Colleges founded before the...
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
Scientists and Engineers for America
-Mission statement:The organization's mission statement states:-SHARP Network:The Science, Health and Related Policies Network is a wiki to track congressional representatives, senators, and candidates as well as presidential candidates....
, an organization focused on promoting sound science in American government.
Key papers
Norepinephrine stimulated increase of cyclic AMP levels in developing mouse brain cell cultures. Science. 1971 Oct 15;174(6):292. PMID 4330303.Regulation of adenosine 3',5'-cyclic monophosphate metabolism in cultured neuroblastoma cells. Nature. 1971 Dec 10;234(5328):356-8. PMID 4332686.
Fluorescent modification of adenosine 3',5'-monophosphate: spectroscopic properties and activity in enzyme systems. Science. 1972 Jul 21;177(45):279-80. PMID 4339302.
The regulatory component of adenylate cyclase. Purification and properties. J Biol Chem. 1981 Nov 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 Dec 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 Jan 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 Oct 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 Jun 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 Sep 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 Sep 25;258(18):11369-76. PMID 6309844.
Homologies between signal transducing G proteins and ras gene products. Science. 1984 Nov 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 Sep 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 Feb 10;243(4892):804-7. PMID 2536957.
Adenylyl cyclase amino acid sequence: possible channel- or transporter-like structure. Science. 1989 Jun 30;244(4912):1558-64. PMID 2472670.
Type-specific regulation of adenylyl cyclase by G protein beta gamma subunits. Science. 1991 Dec 6;254(5037):1500-3. PMID 1962211.
Inhibition of adenylyl cyclase by Gi alpha. Science. 1993 Jul 9;261(5118):218-21. PMID 8327893.
Recombinant G-protein beta gamma-subunits activate the muscarinic-gated atrial potassium channel. Nature. 1994 Mar 17;368(6468):255-7. PMID 8145826.
Structures of active conformations of Gi alpha 1 and the mechanism of GTP hydrolysis. Science. 1994 Sep 2;265(5177):1405-12. PMID 8073283.
Construction of a soluble adenylyl cyclase activated by Gs alpha and forskolin. Science. 1995 Jun 23;268(5218):1769-72. PMID 7792604.
Tertiary and quaternary structural changes in Gi alpha 1 induced by GTP hydrolysis. Science. 1995 Nov 10;270(5238):954-60. PMID 7481799.
The structure of the G protein heterotrimer Gi alpha 1 beta 1 gamma 2. Cell. 1995 Dec 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 Aug 9;86(3):445-52. PMID 8756726.
Crystal structure of the adenylyl cyclase activator Gsalpha. Science. 1997 Dec 12;278(5345):1943-7. PMID 9395396.
Crystal structure of the catalytic domains of adenylyl cyclase in a complex with Gsalpha.GTPgammaS. Science. 1997 Dec 12;278(5345):1907-16. PMID 9417641.
Further reading
- The crystal structure of β2-adrenergic receptor, a classic GPCR was at last revealed.(Nature)(Retrieved on 26 Nov. 2007)
- Authors' summary on the structure (Science) (Retrieved on 26 Nov. 2007)