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[핫이슈] 2012년 노벨 화학상
[핫이슈] 2012년 노벨 화학상 저자 BRIC (생물학연구정보센터)
등록일 2012.10.11
조회 6446  인쇄하기 주소복사 트위터 공유 페이스북 공유 
키워드: 핫이슈, 노벨화학상

The Nobel Prize in Chemistry 2012
 


The Nobel Prize in Chemistry 2012 was awarded jointly to Robert J. Lefkowitz and Brian K. Kobilka "for studies of G-protein-coupled receptors"

기획 및 구성 : 김수정


스웨덴 왕립과학원 노벨위원회는 로버트 J 레프코위츠 듀크대 메디컬센터 교수(69)와 브라이언 K 코빌카 스탠퍼드 의과대 교수(57)를 “G단백질 수용체의 내부작용을 밝히는 획기적 발견”으로 2012년 노벨화학상 수상자로 선정했다고 10일 발표했다.

관련뉴스
- 세포 신호전달 단백질 GPCR 발견… 美 레프코위츠-코빌카 노벨화학상 (THE SCIENCE) 2012-10-11
- 노벨 화학상 美 레프코위츠·코빌카 공동 수상 의미 (파이낸셜뉴스) 2012-10-11
- Nobel Prize in Chemistry 2012: Smart Receptors On Cell Surfaces (ScienceDaily) 2012-10-10

About the Nobel prize Laureate




Press Release

The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Chemistry for 2012 to
Robert J. Lefkowitz
Howard Hughes Medical Institute and Duke University Medical Center, Durham, NC, USA
and Brian K. Kobilka
Stanford University School of Medicine, Stanford, CA, USA
"for studies of G-protein-coupled receptors"

Smart receptors on cell surfaces

Your body is a fine-tuned system of interactions between billions of cells. Each cell has tiny receptors that enable it to sense its environment, so it can adapt to new situtations. Robert Lefkowitz and Brian Kobilka are awarded the 2012 Nobel Prize in Chemistry for groundbreaking discoveries that reveal the inner workings of an important family of such receptors: G-protein?coupled receptors.

For a long time, it remained a mystery how cells could sense their environment. Scientists knew that hormones such as adrenalin had powerful effects: increasing blood pressure and making the heart beat faster. They suspected that cell surfaces contained some kind of recipient for hormones. But what these receptors actually consisted of and how they worked remained obscured for most of the 20th Century.

Lefkowitz started to use radioactivity in 1968 in order to trace cells' receptors. He attached an iodine isotope to various hormones, and thanks to the radiation, he managed to unveil several receptors, among those a receptor for adrenalin: β-adrenergic receptor. His team of researchers extracted the receptor from its hiding place in the cell wall and gained an initial understanding of how it works.

The team achieved its next big step during the 1980s. The newly recruited Kobilka accepted the challenge to isolate the gene that codes for the β-adrenergic receptor from the gigantic human genome. His creative approach allowed him to attain his goal. When the researchers analyzed the gene, they discovered that the receptor was similar to one in the eye that captures light. They realized that there is a whole family of receptors that look alike and function in the same manner.

Today this family is referred to as G-protein-coupled receptors. About a thousand genes code for such receptors, for example, for light, flavour, odour, adrenalin, histamine, dopamine and serotonin. About half of all medications achieve their effect through G-protein?coupled receptors.

The studies by Lefkowitz and Kobilka are crucial for understanding how G-protein?coupled receptors function. Furthermore, in 2011, Kobilka achieved another break-through; he and his research team captured an image of the β-adrenergic receptor at the exact moment that it is activated by a hormone and sends a signal into the cell. This image is a molecular masterpiece ? the result of decades of research.

Read more about this year's prize

Popular Information
Scientific Background

내용 출처: http://nobelprize.org/ 


Robert J. Lefkowitz

Biography

Dr. Lefkowitz was born on April 15, 1943 in New York City. He was an undergraduate at Columbia College from which he received a Bachelor of Arts Degree in 1962. He graduated from Columbia University College of Physicians and Surgeons in 1966 with an M.D. Degree. After serving an internship and one year of general medical residency at the College of Physicians and Surgeons, he served as a Clinical and Research Associate at the National Institutes of Health from 1968 to 1970. From 1970 to 1973 he was at the Massachusetts General Hospital in Boston, Massachusetts, where he completed his medical residency and research and clinical training in cardiovascular disease. Upon completing this training in 1973, he was appointed Associate Professor of Medicine and Assistant Professor of Biochemistry at the Duke University Medical Center. In 1977 he was promoted to Professor of Medicine and in 1982 to James B. Duke Professor of Medicine at Duke University. He is also Professor of Biochemistry. He has been an Investigator of the Howard Hughes Medical Institute since 1976 and was an Established Investigator of the American Heart Association from 1973-1976.

Lefkowitz studies receptor biology and signal transduction and is most well known for his detailed characterizations of the sequence, structure and function of the β-adrenergic and related receptors and for the discovery and characterization of the two families of proteins which regulate them, the G-protein coupled receptor kinases (GRKs) and β-arrestins. Lefkowitz made a remarkable contribution in the mid-1980s when he and his colleagues cloned the gene first for the β-adrenergic receptor, and then rapidly thereafter, for a total of 8 adrenergic receptors (receptors for adrenaline and noradrenaline). This led to the seminal discovery that all G protein-coupled receptors (which include the β-adrenergic receptor) have a very similar molecular structure. The structure is defined by an amino acid sequence which weaves its way back and forth across the plasma membrane seven times. Today we know that about 1,000 receptors in the human body belong to this same family. The importance of this is that all of these receptors use the same basic mechanisms so that pharmaceutical researchers now understood how to effectively target the largest receptor family in the human body. Today, as many as 30 to 50 percent of all prescription drugs are designed to "fit" like keys into the similarly structured locks of Lefkowitz' receptors - everything from anti-histamines to ulcer drugs to beta blockers that help relieve hypertension, angina and coronary disease. Lefkowitz is among the most highly cited researchers in the fields of biology, biochemistry, pharmacology, toxicology, and clinical medicine according to Thomson-ISI.

Key Papers

- Mukherjee, C., Caron, M.G., Coverstone, M. and Lefkowitz, R.J. (1975). "Identification of adenylate cyclase-coupled β-adrenergic receptors in frog erythrocytes with (-)[3H]alprenolol". J. Biol. Chem USA 250 (13): 4869-4876. PMID 238972.
- Mukherjee, C., Caron, M.G. and Lefkowitz, R.J. (1975). "Catecholamine-induced subsensitivity of adenylate cyclase associated with loss of beta-adrenergic receptor binding sites". Proc. Natl. Acad. Sci. USA 72 (5): 1945?1949. doi:10.1073/pnas.72.5.1945. PMC 432665. PMID 1057183. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=432665.
- Lefkowitz, R.J., Mullikin, D. and Caron, M.G. (1976). "Regulation of beta-adrenergic receptors by 5'guanylylimidodiphosphate and other purine nucleotides". J. Biol. Chem USA 251 (15): 4688-4692. PMID 947904.
- Williams, L.T. and Lefkowitz, R.J. (1976). "α-adrenergic receptor identification by [3H]dihydroergocryptine binding". Science 192 (4241): 791-793. PMID 4894. more

출처: http://www.lefkolab.org/Lefkowitz_Bio.html
 
Brian K. Kobilka

Dr. Kobilka is Professor of Medicine, Cardiology, and Molecular and Cellular Physiology at Stanford University School of Medicine. He received his undergraduate degree in biology and chemistry from the University of Minnesota, Duluth, and his M.D. degree from Yale University. After his residency in internal medicine at Barnes Hospital, St. Louis, he joined the laboratory of Robert Lefkowitz as a research fellow in cardiology at Duke University, where he was later Assistant Professor in the Department of Medicine before joining the faculty at Stanford.

출처: http://www.hhmi.com/research/investigators/kobilka_bio.html
http://www.debretts.com/people/biographies/browse/g/2055/John+Bertrand.aspx
 

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