The last 10 amino acid residues beyond the hydrophobic motif are critical for the catalytic competence and function of protein kinase Cá*

The last 10 amino acid residues beyond the hydrophobic motif are critical for the catalytic competence and function of protein kinase Cá*

Yeong, Sui Sum, Zhu, Yimin, Smith, Derek, Verma, Chandra, Lim, Wee Guan, Tan, Bee Jen, Li, Qiu Tian, Cheung, Nam Sang, Cai, Minnie, Zhu, Yi-Zhun, Zhou, Shu-Feng, Tan, Seng-Lai and Duan, Wei 2006, The last 10 amino acid residues beyond the hydrophobic motif are critical for the catalytic competence and function of protein kinase Cá*, Journal of biological chemistry, vol. 281, no. 41, pp. 30768-30781.

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Title	The last 10 amino acid residues beyond the hydrophobic motif are critical for the catalytic competence and function of protein kinase Cá*
Formatted title	Last 10 amino acid residues beyond the hydrophobic motif are critical for the catalytic competence and function of protein kinase Cα*
Author(s)	Yeong, Sui Sum Zhu, Yimin Smith, Derek Verma, Chandra Lim, Wee Guan Tan, Bee Jen Li, Qiu Tian Cheung, Nam Sang Cai, Minnie Zhu, Yi-Zhun Zhou, Shu-Feng Tan, Seng-Lai Duan, Wei
Journal name	Journal of biological chemistry
Volume number	281
Issue number	41
Start page	30768
End page	30781
Publisher	American Society for Biochemistry and Molecular Biology
Place of publication	Bethesda, Md
Publication date	2006-10-13
ISSN	0021-9258
Summary	The segment C-terminal to the hydrophobic motif at the V5 domain of protein kinase C (PKC) is the least conserved both in length and in amino acid identity among all PKC isozymes. By generating serial truncation mutants followed by biochemical and functional analyses, we show here that the very C terminus of PKCα is critical in conferring the full catalytic competence to the kinase and for transducing signals in cells. Deletion of one C-terminal amino acid residue caused the loss of ~60% of the catalytic activity of the mutant PKCα, whereas deletion of 10 C-terminal amino acid residues abrogated the catalytic activity of PKCα in immune complex kinase assays. The PKCα C-terminal truncation mutants were found to lose their ability to activate mitogen-activated protein kinase, to rescue apoptosis induced by the inhibition of endogenous PKC in COS cells, and to augment melatonin-stimulated neurite outgrowth. Furthermore, molecular dynamics simulations revealed that the deletion of 1 or 10 C-terminal residues results in the deformation of the V5 domain and the ATP-binding pocket, respectively. Finally, PKCα immunoprecipitated using an antibody against its C terminus had only marginal catalytic activity compared with that of the PKCα immunoprecipitated by an antibody against its N terminus. Therefore, the very C-terminal tail of PKCα is a novel determinant of the catalytic activity of PKC and a promising target for selective modulation of PKCα function. Molecules that bind preferentially to the very C terminus of distinct PKC isozymes and suppress their catalytic activity may constitute a new class of selective inhibitors of PKC.
Language	eng
Field of Research	060199 Biochemistry and Cell Biology not elsewhere classified
HERDC Research category	C1 Refereed article in a scholarly journal
Copyright notice	©2006, American Society for Biochemistry and Molecular Biology, Inc.
Persistent URL	http://hdl.handle.net/10536/DRO/DU:30006524

Document type:	Journal Article
Collection:	School of Medicine

Citation counts:	Cited 11 times in TR Web of Science Cited 5 times in Scopus
Access Statistics:	474 Abstract Views, 0 File Downloads - Detailed Statistics
Created:	Thu, 31 Jul 2008, 10:40:53 EST

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The last 10 amino acid residues beyond the hydrophobic motif are critical for the catalytic competence and function of protein kinase Cá*

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