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The very C-terminus of protein kinase Cepsilon is critical for the full catalytic competence but its hydrophobic motif is dispensable for the interaction with 3-phosphoinositide-dependent kinase-1

Citation

Zhu, Y and Smith, D and Verma, C and Lim, WG and Tan, BJ and Armstrong, JS and Zhou, S and Chan, E and Tan, SL and Zhu, YZ and Cheung, NS and Duan, W, The very C-terminus of protein kinase Cepsilon is critical for the full catalytic competence but its hydrophobic motif is dispensable for the interaction with 3-phosphoinositide-dependent kinase-1, Cellular Signalling, 18, (6) pp. 807-818. ISSN 0898-6568 (2006) [Refereed Article]

DOI: doi:10.1016/j.cellsig.2005.07.005

Abstract

In this article, we explore the role of the C-terminus (V5 domain) of PKC plays in the catalytic competence of the kinase using serial truncations followed by immune-complex kinase assays. Surprisingly, removal of the last seven amino acid residues at the C-terminus of PKC resulted in a PKC-731 mutant with greatly reduced intrinsic catalytic activity while truncation of eight amino acid residues at the C-terminus resulted in a catalytically inactive PKC mutant. Computer modeling and molecular dynamics simulations showed that the last seven and/or eight amino acid residues of PKC were involved in interactions with residues in the catalytic core. Further truncation analyses revealed that the hydrophobic phosphorylation motif was dispensable for the physical interaction between PKC and 3-phosphoinositide-dependent kinase-1 (PDK-1) as the PKC mutant lacking both the turn and the hydrophobic motifs could still be co-immunoprecipitated with PDK-1. These results provide fresh insights into the biochemical and structural basis underlying the isozyme-specific regulation of PKC and suggest that the very C-termini of PKCs constitute a promising new target for the development of novel isozyme-specific inhibitors of PKC.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Cellular Nervous System
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
Author:Cheung, NS (Dr Nam Cheung)
ID Code:61595
Year Published:2006
Web of Science® Times Cited:8
Deposited By:Menzies Institute for Medical Research
Deposited On:2010-03-04
Last Modified:2010-05-03
Downloads:0

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