A brain-specific activator of cyclin-dependent kinase 5

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

*Corresponding author for this work

Research output: Contribution to journalArticle

517 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)423-426
Number of pages4
JournalNature
Volume371
Issue number6496
DOIs
StatePublished - Jan 1 1994

ASJC Scopus subject areas

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    Lew, J., Huang, Q. Q., Qi, Z., Winkfein, R. J., Aebersold, R., Hunt, T., & Wang, J. H. (1994). A brain-specific activator of cyclin-dependent kinase 5. Nature, 371(6496), 423-426. https://doi.org/10.1038/371423a0