Yet, as demonstrated by Fischer and Ullsperger (2013), we are likely to converge on a common understanding the neural bases of higher cognitive functions from many different paths. “
“We lost a star scientist this summer, Tony Pawson, who made incredible selleck products contributions in his shortened career to our understanding of the biochemical mechanisms of cell signaling. Tony, a Canadian of British origin, performed groundbreaking research spanning nearly 40 years that provided

tremendous insight into how biochemical signals communicate information both between and inside cells. He was the first to recognize that the transduction of these biochemical signals often involve strong noncovalent protein-protein interactions formed by highly conserved noncatalytic domain segments of signaling molecules, the prototype being the Src homology 2 “SH2” domain that he and graduate student Ivan Sadowski first coined back in the 1980s during early work on the oncogenic v-fps protein encoded by the Fujinami sarcoma virus (Sadowski et al., 1986). Tony subsequently selleck chemicals llc demonstrated that these SH2 domains bound with high affinity to select phosphotyrosine-containing motifs in their target proteins, the first report being a landmark paper published in 1990 (Anderson et al., 1990). These crucial findings were rapidly confirmed and expanded upon by Tony’s group and many other laboratories in the 1990s. The biological significance of

the SH2 domain in neurobiology was first uncovered by Tony utilizing the power of Drosophila genetics. Here, graduate student Paul Olivier investigated how the small protein Drk (aka Grb2), consisting of only SH2 and SH3 domains and no inherent catalytic activity, could have such a profound effect on R7 photoreceptor cell development—and made the intriguing discovery that the sole function of this protein was to act as an “adaptor” molecule that connected the Sevenless receptor tyrosine kinase to Ras signaling inside of the cell ( Olivier et al., 1993). Because of

Tony’s groundbreaking research on the SH2 domain, we all now understand that essential chemical signals initiated by catalytic proteins, such as tyrosine kinases and Ras-type GTPases, involves a complex array of protein-protein Phosphatidylinositol diacylglycerol-lyase interactions mediated by distinct protein module “adaptor” domains that function to regulate signaling networks ( Pawson, 1995). We now all take for granted the diverse group of protein-protein interaction modules like the SH2, SH3, PTB, 14-3-3, PDZ, WW, SAM, LIM, PH, and BAR domains that provide a central framework for how biochemical information is propagated. We must remember that Tony was the pioneer. Tony Pawson enjoying a family vacation in Greve, Tuscany. Photo contributed by his daughter, Catherine Pawson. Though originally focused on cancer research, the ramifications of Tony’s work spans all fields of biology and life sciences.