Deciphering protein kinase specificity through large-scale analysis of yeast phosphorylation site motifs

Phosphorylation is a universal mechanism for regulating cell behavior in eukaryotes. Although protein kinases target short linear sequence motifs on their substrates, the rules for kinase substrate recognition are not completely understood. We used a rapid peptide screening approach to determine consensus phosphorylation site motifs targeted by 61 of the 122 kinases in Saccharomyces cerevisiae. By correlating these motifs with kinase primary sequence, we uncovered previously unappreciated rules for determining specificity within the kinase family, including a residue determining P–3 arginine specificity among members of the CMGC [CDK (cyclin-dependent kinase), MAPK (mitogen-activated protein kinase), GSK (glycogen synthase kinase), and CDK-like] group of kinases. Furthermore, computational scanning of the yeast proteome enabled the prediction of thousands of new kinase-substrate relationships. We experimentally verified several candidate substrates of the Prk1 family of kinases in vitro and in vivo and identified a protein substrate of the kinase Vhs1. Together, these results elucidate how kinase catalytic domains recognize their phosphorylation targets and suggest general avenues for the identification of previously unknown kinase substrates across eukaryotes

Social Darwinism in Anglophone Academic Journals: A Contribution to the History of the Term

This essay is a partial history of the term ‘Social Darwinism’. Using large electronic databases, it is shown that the use of the term in leading Anglophone academic journals was rare up to the 1940s. Citations of the term were generally disapproving of the racist or imperialist ideologies with which it was associated. Neither Herbert Spencer nor William Graham Sumner were described as Social Darwinists in this early literature. Talcott Parsons (1932, 1934, 1937) extended the meaning of the term to describe any extensive use of ideas from biology in the social sciences. Subsequently, Richard Hofstadter (1944) gave the use of the term a huge boost, in the context of a global anti-fascist war.Peer reviewe