Profile of Philip Cohen

Abstract

Sir Philip Cohen, a biochemist elected as a foreign associate to the National Academy of Sciences in 2008, remembers the moment in his distinguished career when his studies in cell signaling and protein phosphorylation took off. The moment arrived during a 1978 seminar given by Thomas Vanaman at the University of Dundee (Dundee, Scotland, UK). At that time, Cohen had been working on the first kinase to be studied, phosphorylase kinase, which helps to regulate the breakdown of glycogen. Cohen had purified the kinase to study how it was regulated by cAMP and calcium, but he could not untangle the mechanisms by which calcium activated it. That afternoon, Vanaman spoke about work he had done on calmodulin, a calcium-binding protein and a known intermediary in calcium-regulated processes. Vanaman's descriptions of calmodulin—its small size and heat stability—gave Cohen a better idea of the perplexing faint blue smear that he had observed at the bottom of his polyacrylamide gels. Cohen had been so focused on the massive kinase subunits controlled by cAMP that he had missed the small protein that ran off the end of the gel. Philip Cohen Rushing back to his laboratory after Vanaman's seminar, Cohen prepared a different type of gel and identified a small band ahead of the dye front—a band that appeared even after the sample had been boiled, indicating the component was heat-stable. “Then I knew what the answer was going to be,” Cohen said. “This must be the missing component.” Shortly after, Cohen's hypothesis was confirmed: calmodulin mediated the action of calcium ions on phosphorylase kinase. Cohen has remained at the University of Dundee since 1971 and has worked on many areas of signal transduction, from protein phosphorylation to ubiquitination. His inaugural article, published in a recent issue of PNAS, identifies the phosphorylation sites on Pellino that activate this signaling protein that controls ubiquitination events in the innate immune system (1).