Tony Pawson: In Memoriam

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 interactions mediated by distinct protein module "adaptor" domains that function to regulate signaling networks (Pawson, 1995). The idea that bidirectional cell-cell--or more precisely axon-cell--contact-mediated Eph-Ephrin interactions help instruct the wiring of the brain set the stage for our understanding how this large family of interacting receptors and ligands controls all sorts of cellular migration/adhesion-type events, including neuronal migration, synapse formation, and synaptic plasticity in the brain; the regulation of blood vessel growth throughout the body; midline development of the embryo; and of course stem cell biology.