AI Article Synopsis
- D-type cyclin-dependent kinases (Cdk4 and Cdk6) are essential for the transition from G1 to S phase in the cell cycle, but they may serve different roles despite being biochemically similar.
- In vitro studies reveal that Cdk4 and Cdk6 preferentially phosphorylate different residues in the retinoblastoma protein (pRB), with Cdk6 favoring Thr821 and Cdk4 favoring Thr826.
- This suggests that distinct substrate specificities of Cdk4 and Cdk6 could explain their unique functions in regulating cellular processes, and that the Cdk enzymes themselves play a role in recognizing their substrates.
Article Abstract
D-type cyclin-dependent kinases (Cdk4 and Cdk6) regulate the G1 to S phase progression of the mammalian cell cycle. It has been suggested that Cdk4 and Cdk6 may have distinct functions in vivo, even though they are indistinguishable biochemically. Here we show that although these Cdks phosphorylate multiple residues in pRB, they do so with different residue selectivities in vitro; Thr821 and Thr826 are preferentially phosphorylated by Cdk6 and Cdk4, respectively. This raises the possibility different substrate specificities lead to their different roles in the regulation of cellular events. Furthermore, our results indicate the new concept that Cdk itself contributes to substrate recognition.
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