The C-terminus of PRK2/PKNγ is required for optimal activation by RhoA in a GTP-dependent manner

Lim, Wee Guan, Chen, Xiao, Liu, Jun-Ping, Tan, Bee Jen, Zhou, Shufeng, Smith, Adam, Lees, Nathaniel, Hou, Liansheng, Gu, Fukang, Yu, Xi Yong, Du, Yaomin, Smith, Derek, Verma, Chandra, Liu, Ke and Duan, Wei 2008, The C-terminus of PRK2/PKNγ is required for optimal activation by RhoA in a GTP-dependent manner, Archives of biochemistry and biophysics, vol. 479, no. 2, pp. 170-178.

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Title The C-terminus of PRK2/PKNγ is required for optimal activation by RhoA in a GTP-dependent manner
Author(s) Lim, Wee Guan
Chen, Xiao
Liu, Jun-Ping
Tan, Bee Jen
Zhou, Shufeng
Smith, Adam
Lees, Nathaniel
Hou, Liansheng
Gu, Fukang
Yu, Xi Yong
Du, Yaomin
Smith, Derek
Verma, Chandra
Liu, Ke
Duan, Wei
Journal name Archives of biochemistry and biophysics
Volume number 479
Issue number 2
Start page 170
End page 178
Total pages 9
Publisher Academic Press
Place of publication New York, N.Y.
Publication date 2008-11-15
ISSN 0003-9861
1096-0384
Keyword(s) PRK2
PKC
Rho
PDK-1
signal transduction
Summary PRK2/PKNγ is a Rho effector and a member of the protein kinase C superfamily of serine/threonine kinases. Here, we explore the structure–function relationship between various motifs in the C-terminal half of PRK2 and its kinase activity and regulation. We report that two threonine residues at conserved phosphoacceptor position in the activation loop and the turn motif are essential for the catalytic activity of PRK2, but the phosphomimetic Asp-978 at hydrophobic motif is dispensable for kinase catalytic  competence. Moreover, the PRK2-Δ958 mutant with the turn motif truncated still interacts with 3-phosphoinositide-dependent kinase-1 (PDK-1). Thus, both the intact hydrophobic motif and the turn motif in PRK2 are dispensable for the binding of PDK-1. We also found that while the last seven amino acid residues at the C-terminus of PRK2 are not required for the activation of the kinase by RhoA in vitro, however, the extreme C-terminal segment is critical for the full activation of PRK2 by RhoA in cells in a GTP-dependent manner. Our data suggest that the extreme C-terminus of PRK2 may represent a potential drug target for effector-specific pharmacological intervention of Rho-medicated biological processes.
Language eng
Field of Research 060199 Biochemistry and Cell Biology not elsewhere classified
Socio Economic Objective 929999 Health not elsewhere classified
HERDC Research category C1 Refereed article in a scholarly journal
HERDC collection year 2008
Copyright notice ©2008, Elsevier Inc
Persistent URL http://hdl.handle.net/10536/DRO/DU:30017725

Document type: Journal Article
Collection: School of Medicine
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