The scientific community has been saddened by the untimely passing of Tony Pawson, a pre-eminent investigator in the signal transduction field over the past three decades. He was born in Maidstone, Kent, UK, in 1952 and went to school at the Winchester College. After reading biochemistry at Clare College, University of Cambridge, he obtained his PhD in molecular virology from Imperial Cancer Research Fund Laboratories under the supervision of Alan E. Smith. In 1976 Tony moved to North America, initially working with Steve Martin at the University of California, Berkeley, USA, on molecular and cellular aspects of cell transformation. These studies fostered in him a longstanding interest in the molecular origins of cellular transformation and cancer progression. They also laid the foundation for his own independent research program that began in the early 1980s at the University of British Columbia in Vancouver, Canada, and moved in 1985 to the Samuel Lunenfeld Research Institute at the Mount Sinai Hospital in Toronto. He remained there for the rest of his life and was instrumental in invigorating Canadian cellular biochemistry through his many discoveries, prudent recruitment and mentoring of junior colleagues. His tireless efforts to promote science in Canada have shaped the region and helped to make Toronto a world-renowned centre for cell signalling research.
Tony's most important discovery was discerning a molecular mechanism of signal transduction that involves the establishment of complexes of signalling molecules that are held together by specific protein–protein interaction domains. Tony unravelled this mechanism by studying the oncogenic tyrosine kinase v-Fps. He found that this enzyme contains structures outside the kinase domain that are necessary for its transforming activity. This finding led to the discovery of the SH2 and SH3 domains that are found in a broad range of signal transduction molecules, including protein kinases, phosphatases and adaptors. Furthermore, Tony showed that the SH2 domain binds tyrosine-phosphorylated residues in proteins, and that, for instance, phospholipase C-γ and Ras-GAP use their SH2 domains to bind to specific phosphorylated tyrosine residues in the activated platelet-derived growth factor and epidermal growth factor receptors. He also provided important insights into the structural basis for the selectivity of SH2 binding, which is crucial for specificity in signal transduction.
