Regulation of cyclin-dependent kinase 5 catalytic activity by phosphorylation

摘要: Cyclin-dependent kinase 5 (cdk5) is found in an active form only neuronal cells. Activation by virtue of association with the cyclin-like proteins p35 (or its truncated p25) and p39 mechanism currently shown to regulate cdk5 catalytic activity. In addition cyclin binding, other members cdk family require for maximal activation phosphorylation a Ser/Thr residue (Thr160 case cdk-2) that conserved all cdks except cdk8. This site phosphorylated cdk-activating kinases, which, however, do not phosphorylate cdk5. To examine possible existence phosphorylation-dependent regulatory cdk5, we have metabolically labeled PC12 cells 32Pi endogenous phosphorylated. Bacterially expressed also can be cell lysates. Phosphorylation lysate results significant increase cdk5/p25 Ser159 homologous Thr160 cdk2. A Ser159-to-Ala (S159A) mutant did show similar activation, which suggests regulated at this site. Like family, activity influenced both p25 binding phosphorylation. We cdk5-activating (cdk5AK) distinct from (cyclin H/cdk7) was reported previously neither nor affect casein I, but II, activate vitro.