Cak1 Background Information A family of protein kinases known as cyclin-dependent kinases (Cdks) mediate Eukaryotic cell cycle progression (1). Cdk-activating kinase (CAK1) phosphorylates the major S. cerevisiae Cdk, Cdc28p, at threonine-169 allowing it to bind tightly to cyclin (1). This activation pathway contrasts with that in higher eukaryotes, in which cyclin binding appears to precede activating phosphorylation (1). CAK1 is a monomeric protein kinase with unique properties shared by Csk1 in S. Pombe, Cak1 in Candida Albicans and Cak1At in Arabidopsis Thaliana (2). All of these kinases display a preference for cyclin-free Cdk substrates, are insensitive to the protein kinase inhibitor 5’-FSBA and to the mutation of a highly conserved lysine residue found in the nucleotide binding pocket of all protein kinases (2). CAK1 also targets Bur1 which is part of a Cdk complex in S. cerevisiae that is involved in transcriptional regulation (4). CAK1 is required for spore wall assembly and mutants lacking CAK1 are blocked early in meiotic development due to substantial delays in premeiotic DNA synthesis and defects in the expression of sporulation-specific genes, including IME1 (3,5). CAK1 activates multiple steps in meiotic development through the activation of various protein kinase targets (3).
