A brain-specific activator of cyclin-dependent kinase 5.
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. We have purified a novel Cdc2-like kinase from bovine brain capable of phosphorylating both the neurofilament proteins and tau. The purified enzyme is a heterodimer of cyclin-dependent kinase 5 (Cdk5) and a novel regulatory subunit, p25 (ref. 8). When overexpressed 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 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.
Lew
J
J
MRC Group in Signal Transduction, University of Calgary, Alberta, Canada.
Huang
Q Q
QQ
Qi
Z
Z
Winkfein
R J
RJ
Aebersold
R
R
Hunt
T
T
Wang
J H
JH
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D001921:Brain / Q000201:enzymology*; D002417:Cattle; D003001:Cloning, Molecular; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases; D004247:DNA; D004789:Enzyme Activation; D004926:Escherichia coli; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D016900:Neurofilament Proteins / Q000378:metabolism; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D016875:tau Proteins / Q000378:metabolism
D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; C089495:neuronal Cdk5 activator (p25-p35); D016875:tau Proteins; D004247:DNA; D051360:Cyclin-Dependent Kinase 5; D017346:Protein Serine-Threonine Kinases; C495905:CDK5 protein, human; D018844:Cyclin-Dependent Kinases