Abstract:
:PRK1/PKN is a member of the protein kinase C (PKC) superfamily of serine/threonine protein kinases. Despite its important role as a RhoA effector, limited information is available regarding how this kinase is regulated. We show here that the last seven amino acid residues at the C-terminus is dispensable for the catalytic activity of PRK1 but is critical for the in vivo stability of this kinase. Surprisingly, the intact hydrophobic motif in PRK1 is dispensable for 3-phosphoinositide-dependent kinase-1 (PDK-1) binding and phosphorylation of the activation loop, as the PRK1-Delta940 mutant lacking the last two residues of the hydrophobic motif and the last 5 residues at the C-terminus interacts with PDK-1 in vivo and has a similar specific activity as the wild-type protein. We also found that the last four amino acid residues at the C-terminus of PRK1 is critical for the full lipid responsiveness as the PRK1-Delta942 deletion mutant is no longer activated by arachidonic acid. Our data suggest that the very C-terminus in PRK1 is critically involved in the control of the catalytic activity and activation by lipids. Since this very C-terminal segment is the least conserved among members of the PKC superfamily, it would be a promising target for isozyme-specific pharmaceutical interventions.
journal_name
Cell Signaljournal_title
Cellular signallingauthors
Lim WG,Zhu Y,Wang CH,Tan BJ,Armstrong JS,Dokland T,Yang H,Zhu YZ,Teo TS,Duan Wdoi
10.1016/j.cellsig.2004.12.003subject
Has Abstractpub_date
2005-09-01 00:00:00pages
1084-97issue
9eissn
0898-6568issn
1873-3913pii
S0898-6568(04)00281-5journal_volume
17pub_type
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