PHOSPHORYLATION of the neurofilament proteins of high and medium relative molecular mass, as well as of the Alzheimer's tau protein, is thought to be catalysed by a protein kinase with Cdc2-like substrate specificity 1-7. We have purified a novel Cdc2-like kinase from bovine brain 8 capable of phosphorylating both the neurofilament proteins 9 and tau10. The purified enzyme is a hetero-dimer of cyclin-dependent kinase 5 (Cdk5)9 and a novel regulatory subunit, p25 (ref. 8). When overexpressed and purified from Esch-erichia coli, p25 can activate Cdk5 in vitro. Unlike Cdk5, which is ubiquitously expressed in human tissue, the p25 transcript is expressed only in brain. A full-length complementary DNA clone showed that p25 is a truncated form of a larger protein precursor, p35, which seems to be the predominant form of the protein in crude brain extract. Cdk5/p35 is the first example of a Cdc2-like kinase with neuronal function.
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