A BRAIN-SPECIFIC ACTIVATOR OF CYCLIN-DEPENDENT KINASE-5

PHOSPHORYLATION of the neurofilament proteins of high and medium relat ive molecular mass, as well as of the Alzheimer's tau protein, is thou ght to be catalysed by a protein kinase with Cdc2-like substrate speci ficity(1-7). We have purified a novel Cdc2-like kinase from bovine bra in(8) capable of phosphorylating both the neurofilament proteins(9) an d tau(10). The purified enzyme is a heterodimer of cyclin-dependent ki nase 5 (Cdk5)(9) and a novel regulatory subunit, p25 (ref. 8). When ov erexpressed and purified from Escherichia 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 complem entary DNA clone showed that p25 is a truncated form of a larger prote in precursor, p35, which seems to be the predominant form of the prote in in crude brain extract. Cdk5/p35 is the first example of a Cdc2-lik e kinase with neuronal function.