Activation of RAC-protein kinase by heat shock and hyperosmolarity stress through a pathway independent of phosphatidylinositol 3-kinase

Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7639-43. doi: 10.1073/pnas.93.15.7639.

Abstract

RAC protein kinase (RAC-PK), a serine/threonine protein kinase containing a pleckstrin homology (PH) domain, was activated by cellular stress such as heat shock and hyperosmolarity. Wortmannin, which is known as a potent inhibitor of phosphatidylinositol 3-kinase and normally inhibits growth factor-induced activation of RAC-PK, did not suppress heat-shock induced activation of RAC-PK, indicating that this stress-induced activation of the kinase is not mediated by phosphatidylinositol 3-kinase. The PH domain was indispensable for stress-induced activation of RAC PK. In heat-treated cells, PKC delta, a member of the protein kinase C family, was found to associate with the PH domain of RAC-PK. This PKC subspecies was phosphorylated in vitro by RAC-PK. The results suggest that RAC-PK may play a role in the cellular response to stress through its PH domain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Androstadienes / pharmacology
  • Animals
  • Anisomycin / pharmacology
  • Blood Proteins / chemistry
  • Cell Line
  • Chlorocebus aethiops
  • Cycloheximide / pharmacology
  • Dactinomycin / pharmacology
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • Gene Expression / drug effects
  • Hot Temperature
  • Isoenzymes / metabolism*
  • Mice
  • Oligopeptides
  • Osmolar Concentration
  • Peptides
  • Phosphatidylinositol 3-Kinases
  • Phosphoproteins*
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Platelet-Derived Growth Factor / pharmacology
  • Protein Kinase C / metabolism*
  • Protein Kinase C-delta
  • Protein Serine-Threonine Kinases / biosynthesis*
  • Protein Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins c-akt
  • Rats
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / metabolism
  • Sequence Tagged Sites
  • Sorbitol / pharmacology
  • Stress, Physiological
  • Transfection
  • Wortmannin

Substances

  • Androstadienes
  • Blood Proteins
  • Enzyme Inhibitors
  • Isoenzymes
  • Oligopeptides
  • Peptides
  • Phosphoproteins
  • Platelet-Derived Growth Factor
  • Recombinant Proteins
  • platelet protein P47
  • Dactinomycin
  • Sorbitol
  • Anisomycin
  • Cycloheximide
  • FLAG peptide
  • Phosphotransferases (Alcohol Group Acceptor)
  • Prkcd protein, mouse
  • Prkcd protein, rat
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Protein Kinase C
  • Protein Kinase C-delta
  • Wortmannin