2008Basic SciencesLife Sciences (Molecular Biology, Cell Biology, Neurobiology)
Anthony James Pawson photo

Anthony James Pawson

  • Canada, U.K. / 1952-2013
  • Molecular Biologist
  • Distinguished Investigator, Samuel Lunenfeld Research Institute of Mount Sinai Hospital ; University Professor, University of Toronto

Proposing and Proving the Concept of Adapter Molecules in the Signal Transduction

Dr. Pawson proposed and proved the concept that the unique adapter structure exists in signaling proteins, and that the binding of adapters to specific phosphotyrosine-containing domains induces cascades of intracellular signaling that controls cellular growth and differentiation. This concept has established one of the basic paradigms of signal transduction and significantly contributed to the subsequent development in life sciences.

Profile

Brief Biography

1952
Born in Maidstone, U.K.
1976
Ph.D. (Molecular Biology), London University
1976
Postdoctoral Research Fellow, University of California, Berkeley
1981
Assistant Professor, Department of Microbiology, The University of British Columbia
1985
Senior Investigator, Samuel Lunenfeld Research Institute, Mount Sinai Hospital
1985
Associate Professor, Department of Medical Genetics and Microbiology, University of Toronto
1989
Full Professor, Department of Medical Genetics and Microbiology (now Department of Molecular Genetics), University of Toronto
1998
University Professor, University of Toronto
2000
Director of Research, Samuel Lunenfeld Research Institute, Mount Sinai Hospital
2006
Distinguished Investigator, Samuel Lunenfeld Research Institute, Mount Sinai Hospital

Selected Awards and Honors

1994
International Award, Gairdner Foundation
2000
Officer of the Order of Canada
2005
Wolf Foundation Prize in Medicine, Wolf Foundation
2005
The Royal Medal, Royal Society of London
2006
Order of the Companions of Honour
Member:
Royal Society of London, Royal Society of Canada, National Academy of Sciences, American Academy of Arts and Sciences

Selected Publications

1984

Identification of functional regions in the transforming protein of Fujinami sarcoma virus by in-phase insertion mutagenesis (Stone, J. C., Atkinson, T., Smith, M. E. and Pawson, T.). Cell 37: 549-558, 1984.

1986

A noncatalytic domain conserved among cytoplasmic protein-tyrosine kinases modifies the kinase function and transforming activity of Fujinami sarcoma virus P130gag-fps (Sadowski, I., Stone, J. C. and Pawson, T.). Molecular Cellular Biology 6: 4396-4408, 1986.

1990

Binding of SH2 domains of phospholipase Cγ1, GAP and Src to activated growth factor receptors (Anderson, D., Koch, C. A., Grey, L., Ellis, C., Moran, M. F. and Pawson, T.). Science 250: 979-982, 1990.

1990

Src homology region 2 domains direct protein-protein interactions in signal transduction (Moran, M., Koch, C. A., Anderson, D., Ellis, L., England, L., Martin, G. S. and Pawson, T.). Proceeding National Academy of Sciences, U.S.A. 87: 8622-8626, 1990.

Citation

Proposing and Proving the Concept of Adapter Molecules in the Signal Transduction

Dr. Anthony James Pawson discovered a new mechanism of intracellular signal transduction, revealing an important molecular infrastructure that controls cellular growth and differentiation. In the late 1970s, the autophosphorylation of oncogene products and growth factor receptors was found at specific tyrosine residues, but the molecular mechanism of signal transduction beyond tyrosine phosphorylation remained unknown. Dr. Pawson demonstrated that intracellular signaling proteins carry a domain with a unique modular structure, which he termed Src homology 2 (SH2), and that this domain recognizes and binds the phosphotyrosine and the flanking amino acids of target molecules to induce cascades of intracellular signaling that facilitates cellular growth and differentiation.

Based on his finding that not only the catalytic domains (tyrosine kinases) but also the flanking domains in oncogene products are necessary for the transformation (i.e., cancer-like behavior) of cells, Dr. Pawson discovered that oncogene products and signaling proteins share a common sequence consisting of approximately 100 amino acid residues, which he termed SH2, and that the SH2 domain takes part in the interaction between tyrosine kinases and their substrates. He proposed that SH2 domains act as adapters that mediate the binding with cell membrane receptors and cytoskeletal proteins, by showing for the first time that there is a protein that can bind to the phosphotyrosine of a signaling protein, RasGAP. He disclosed that various SH2 domains can directly bind tyrosine-phosphorylated proteins in vitro. Furthermore, he demonstrated that the binding strength between SH2 domains and their target proteins varies, explaining that each SH2 domain binds to a specific tyrosine-phosphorylated protein to induce specific intracellular signaling cascades.

These achievements by Dr. Pawson laid out the scheme that adapter molecules facilitate successive protein-protein associations like the Lego blocks, thereby participating in the fundamental mechanism of signal transduction that controls cellular growth and differentiation, as well as development of cancer. Consequently, the proposal and proof of the concept for adapter molecules by Dr. Pawson have established one of the basic paradigms in signal transduction and contributed significantly to the subsequent development in life sciences.

For these reasons, the Inamori Foundation is pleased to present the 2008 Kyoto Prize in Basic Sciences to Dr. Anthony James Pawson.

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Lecture

Abstract of the Lecture

Thinking about how living things work

I have been fascinated since I was young by the idea that we can use the tools of science to understand how living creatures work, and I can still vividly remember the moment when this notion forcibly struck me as a real possibility, thanks to the persuasive words of a biology teacher. Human beings all start life as a single cell, and indeed we can think of the cell as the basic unit of life — how cells function, how they evolve to become more complex, how they cooperate with one another to make structures such as the human brain, and what goes wrong with the cellular machinery in diseases like cancer, are questions that have gripped me with a passion. My first academic love was for classical languages such as Latin and Greek, and curiously our work on the proteins that organize cellular behaviour has revealed a kind of molecular language through which cells communicate with one another. Proteins are the functional molecules that execute the instructions implicit in the DNA, and are responsible for building cells and tissues, and controlling their behaviour. They are the targets of most therapeutic drugs, and aberrations in their functions underlie disease. We now realize that proteins are built from smaller blocks, rather like a childfs building toy, many of which serve to link proteins one to another. This creates a communications network within the cell, through which it exchanges signals with its neighbours.

We have seen extraordinary advances in our understanding of the molecular basis for life, and we tend to think that we are deeply knowledgeable about human physiology and disease. But I would argue that we are still profoundly ignorant of how cells work; how living things work. The fun and excitement in biology is just starting. I believe that nothing is more important to us human beings than to know where we came from, and how we relate to the vast diversity of other species on the planet.

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Workshop

Workshop

Signal Network in Biological Functions

date
13:00 - 17:00, November 12, 2008 (Wed.)
palce
Kyoto International Conference Center
Coordinator
Shigetada Nakanishi (Chairman, Kyoto Prize Committee; Director, Osaka Bioscience Institute)
Coordinator/Moderator
Kozo Kaibuchi (Member, Kyoto Prize Selection Committee; Professor, Graduate School of Medicine, Nagoya University)
Organized by Inamori Foundation
Supported by Kyoto Prefectural Government, Kyoto City Government, and NHK
With the cooperation of The Japan Neuroscience Society, Japan Society for Cell Biology, The Japanese Biochemical Society, The Japanese Cancer Association, The Molecular Biology Society of Japan

Program

13:00
Opening Address Shigetada Nakanishi
Introduction of Laureate Kozo Kaibuchi
Laureate Lecture Anthony James Pawson (the Laureate in Basic Sciences)
"SH2 domains, Adapters and Tyrosine Kinases: Back to the Future"
Lecture Ryuichi Sakai (Chief, Growth Factor Division, National Cancer Center Research Institute)
"Roles of Phosphotyrosine-Containing Molecules in Tumor Progression"
Intermission
Lecture Michiyuki Matsuda (Professor, Graduate School of Biostudies, Kyoto University)
"Live Cell Imaging of the Growth Signaling Network"
Lecture Kozo Kaibuchi
"Signalling for Cell Polarity"
Lecture Shizuo Akira (Member, Kyoto Prize Selection Committee; Director, WPI Immunology Frontier Research Center, Osaka University)
"Pathogen Recognition: Receptors and Signaling"
17:00
Closing
PAGETOP