Frank McCormick
Alfred Wittinghofer and his group of structural biologists and biochemists laid the groundwork for developing drugs that target RAS, from the first structure of a RAS protein in its active state, through to a deep understanding of RAS function and regulation. Their fundamental discoveries include the mechanisms of hydrolysis and nucleotide exchange, effector engagement and subcellular localization. In this review, I share some of the highlights of years of a friendship and collaboration for the many years during which Fred's group led the field and helped understand and defeat the "beating heart of signal transduction".