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

Zhu, Yimin, Smith, Derek, Verma, Chandra, Lim, Wee Guan, Tan, Bee Jen, Armstrong, Jeffrey S., Zhou, Shufeng, Chan, Eli, Tan, Seng-Lai, Zhu, Yi-Zhun, Cheung, Nam Sang and Duan, Wei 2006, The very C-terminus of protein kinase CĹ is critical for the full catalytic competence but its hydrophobic motif is dispensable for the interaction with 3-phosphoinositide-dependent kinase-1, Cellular signalling, vol. 18, no. 6, pp. 807-818.

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Title The very C-terminus of protein kinase CĹ is critical for the full catalytic competence but its hydrophobic motif is dispensable for the interaction with 3-phosphoinositide-dependent kinase-1
Author(s) Zhu, Yimin
Smith, Derek
Verma, Chandra
Lim, Wee Guan
Tan, Bee Jen
Armstrong, Jeffrey S.
Zhou, Shufeng
Chan, Eli
Tan, Seng-Lai
Zhu, Yi-Zhun
Cheung, Nam Sang
Duan, Wei
Journal name Cellular signalling
Volume number 18
Issue number 6
Start page 807
End page 818
Publisher Elsvier Inc.
Place of publication Amsterdam, Netherlands
Publication date 2006-06
ISSN 0898-6568
Keyword(s) PKCvar epsilon
PDK-1
Phosphorylation
signal transduction
Hydrophobic motif
V5 domain
Summary In this article, we explore the role of the C-terminus (V5 domain) of PKCvar epsilon 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 PKCvar epsilon resulted in a PKCvar epsilon-Δ731 mutant with greatly reduced intrinsic catalytic activity while truncation of eight amino acid residues at the C-terminus resulted in a catalytically inactive PKCvar epsilon mutant. Computer modeling and molecular dynamics simulations showed that the last seven and/or eight amino acid residues of PKCvar epsilon 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 PKCvar epsilon and 3-phosphoinositide-dependent kinase-1 (PDK-1) as the PKCvar epsilon 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.
Language eng
Field of Research 060199 Biochemistry and Cell Biology not elsewhere classified
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2005, Elsevier Inc.
Persistent URL http://hdl.handle.net/10536/DRO/DU:30006556

Document type: Journal Article
Collection: School of Medicine
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