Regulation of cyclin D-dependent kinase 4 (cdk4) by cdk4-activating kinase.

摘要: The accumulation of assembled holoenzymes composed regulatory D-type cyclins and their catalytic partner, cyclin-dependent kinase 4 (cdk4), is rate limiting for progression through the G1 phase cell cycle in mammalian fibroblasts. Both synthesis assembly cdk4 depend upon serum stimulation, but even when both subunits are ectopically overproduced, they do not assemble into complexes serum-deprived cells. When coexpressed from baculoviral vectors intact Sf9 insect cells, assembles with to form active protein kinases. In contrast, recombinant cyclin produced cells or bacteria as efficiently functional combined vitro can be activated presence lysates obtained proliferating Assembly D-cdk4 coinfected facilitates phosphorylation on threonine 172 by a cdk-activating (CAK). proceed absence this modification, mutants which cannot phosphorylated CAK remain catalytically inactive. Therefore, formation complex bound subunit independently regulated, addition requirement activity, stimulation required promote