RGD Reference Report - Identification of a common protein association region in the neuronal Cdk5 activator. - Rat Genome Database

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Identification of a common protein association region in the neuronal Cdk5 activator.

Authors: Wang, X  Ching, YP  Lam, WH  Qi, Z  Zhang, M  Wang, JH 
Citation: Wang X, etal., J Biol Chem 2000 Oct 13;275(41):31763-9.
RGD ID: 1358279
Pubmed: PMID:10915792   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M004358200   (Journal Full-text)

Cyclin-dependent protein kinase 5 (Cdk5) depends on the association with neuronal Cdk5 activator (Nck5a) for kinase activity. A variety of cellular proteins have been shown to undergo high affinity association with Nck5a, including three novel proteins, C42, C48, and C53 found by a yeast two-hybrid screen (Ching, Y. P., Qi, Z., and Wang, J. H. (2000) Gene 242, 285-294). The three proteins show competitive binding to Nck5a suggesting that they bind at a common site. The binding site has been mapped to a region of 26 amino acid residues (residues 145 to 170) at the N-terminal boundary of the kinase activation domain of Nck5a. This region of Nck5a contains an amphipathic alpha-helix whose hydrophobic face is involved in Cdk5 activation (Chin, K. T., Ohki, S, Tang, D., Cheng, H. C., Wang, J. H. , and Zhang, M. (1999) J. Biol. Chem. 274, 7120-7127). Several lines of evidence suggest that Nck5a interacts with the binding proteins at the hydrophilic face of the amphipathic alpha-helix. First, the Nck5a-(145-170) peptide can bind Cdk5 and Nck5a-binding proteins simultaneously. Second, the association of Nck5a-(145-170) to C48 can be markedly reduced by high ionic strength whereas the interaction between Nck5a and Cdk5 is not affected. Third, substitution of Glu(157) by glutamine in Nck5a-(145-170) abolishes the peptide's ability to bind to the three Nck5a-binding proteins without diminishing its Cdk5 binding activity.



Objects referenced in this article
Gene Cdk5rap1 CDK5 regulatory subunit associated protein 1 Rattus norvegicus
Gene Cdk5rap2 CDK5 regulatory subunit associated protein 2 Rattus norvegicus
Gene Cdk5rap3 CDK5 regulatory subunit associated protein 3 Rattus norvegicus

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