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A brain-specific activator of cyclin-dependent kinase 5

Nature volume 371, pages 423–426 (1994)Cite this article

Abstract

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 specificity1–7. We have purified a novel Cdc2-like kinase from bovine brain8 capable of phosphorylating both the neurofilament proteins9 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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Author notes

  1. Ruedi Aebersold: Biomedical Research Centre and Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada

  2. Tim Hunt: ICRF, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, UK

Authors and Affiliations

  1. MRC Group in Signal Transduction, University of Calgary, 3330 Hospital Drive N. W., Calgary, Alberta, T2N 4N1, Canada

    John Lew, Qi-Quan Huang, Zhong Qi, Robert J. Winkfein, Ruedi Aebersold, Tim Hunt & Jerry H. Wang

Authors
  1. John Lew
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  2. Qi-Quan Huang
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  5. Ruedi Aebersold
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  7. Jerry H. Wang
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Lew, J., Huang, QQ., Qi, Z. et al. A brain-specific activator of cyclin-dependent kinase 5. Nature 371, 423–426 (1994). https://doi.org/10.1038/371423a0

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