Cyclins, cyclin dependent kinases, and regulation of steroid receptor action

Steroid receptors (SR), which are ligand activated transcription factors, and their coactivators are phosphoproteins whose activities are regulated by cell signaling pathways. Many of the identified phosphorylation sites in these proteins contain Ser/Thr-Pro motifs suggesting that they are substrates for cyclin dependent kinases and/or for mitogen activated protein kinases. An analysis of the roles of cyclins and their kinases in regulating receptor action has revealed that there are both stimulatory and inhibitory actions of cyclins, that some of the actions are independent of the partner kinases and that these activities are receptor specific. Consistent with this finding, the limited analyses of receptor activity as a function of cell cycle reveal distinct patterns of activation. SR often regulate cell proliferation. Thus, the cross-talk between cyclins and their kinases and the SR provides a means for integrating the actions of the SR with the cell cycle status of cells.