Recognition of Cdk2 by Cdk7

Abstract

Cdk7, a member of the cyclin dependent protein kinase family, regulates the activities of other Cdks through phosphorylation on their activation segment, and hence contributes to control of the eukaryotic cell cycle. Cdk7 is itself phosphorylated on the activation segment. Cdk7 phosphorylates Cdk1, Cdk2, Cdk4, and Cdk6, but only Cdk1 and Cdk2 can phosphorylate Cdk7 and none of them is able to auto‐phosphorylate. The activation segments of the Cdks are very similar in sequence. Their specificity does not appear to be dictated by the sequences surrounding the phosphorylation sites but by structural determinants at remote sites. Through mutagenesis studies, we have identified regions in Cdk2 responsible for its interaction with Cdk7. A model has been built that explains the molecular basis for the specificity observed in Cdk recognition. The two kinases are arranged in a quasi‐symmetric head‐to‐tail arrangement in which the N‐terminal lobe from one kinase docks against the C‐terminal lobe from the other kinase, and the activation segments are within reach of the opposite catalytic sites. Further experiments demonstrate that cyclin A hydrophobic pocket is not a recruitment site for Cdk7. Proteins 2007.