The last five amino acid residues at the C-terminus of PRK1/PKN is essential for full lipid responsiveness.

Academic Article

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.
  • Authors

    Published In

    Keywords

  • 3-Phosphoinositide-Dependent Protein Kinases, Amino Acid Sequence, Animals, Arachidonic Acid, Aspartic Acid, COS Cells, Catalysis, Cercopithecus aethiops, Enzyme Activation, Enzyme Stability, Hydrophobic and Hydrophilic Interactions, Models, Molecular, Molecular Sequence Data, Mutation, Phenylalanine, Protein Kinase C, Protein Structure, Tertiary, Protein-Serine-Threonine Kinases, Rats, Sequence Alignment
  • Digital Object Identifier (doi)

    Pubmed Id

  • 11684019
  • Author List

  • Lim WG; Zhu Y; Wang C-H; Tan BJ; Armstrong JS; Dokland T; Yang H; Zhu Y-Z; Teo TS; Duan W
  • Start Page

  • 1084
  • End Page

  • 1097
  • Volume

  • 17
  • Issue

  • 9