The product of par-4, a gene induced during apoptosis, interacts selectively with the atypical isoforms of protein kinase C

Cell. 1996 Sep 6;86(5):777-86. doi: 10.1016/s0092-8674(00)80152-x.

Abstract

The atypical PKCs are involved in a number of important cellular functions, including cell proliferation. We report here that the product of the par-4 gene specifically interacts with the regulatory domains of zeta PKC and lambda/LPKC, which dramatically inhibits their enzymatic activity. This is particularly challenging, because expression of par-4 has been shown to correlate with growth inhibition and apoptosis. Results are shown here demonstrating that the expression of par-4 in NIH-3T3 cells induces morphological changes typical of apoptosis, which are abrogated by cotransfection of either wild-type zeta PKC or lambda/LPKC, but not by their respective kinase-inactive mutants. These findings support a role for the atypical PKC subspecies in the control of cell growth and survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Amino Acid Sequence
  • Animals
  • Apoptosis / physiology*
  • Apoptosis Regulatory Proteins
  • Bacterial Proteins / genetics
  • Base Sequence
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Carrier Proteins / pharmacology
  • Cell Line
  • Chlorocebus aethiops
  • Cloning, Molecular
  • Enzyme Inhibitors
  • Humans
  • Intracellular Signaling Peptides and Proteins*
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / metabolism*
  • Mice
  • Molecular Sequence Data
  • Promoter Regions, Genetic / physiology
  • Protein Binding
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism*
  • Protein-Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-mos / metabolism
  • Proto-Oncogene Proteins c-raf
  • Recombinant Fusion Proteins / metabolism
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Serine Endopeptidases / genetics
  • Zinc Fingers

Substances

  • Apoptosis Regulatory Proteins
  • Bacterial Proteins
  • Carrier Proteins
  • Enzyme Inhibitors
  • Intracellular Signaling Peptides and Proteins
  • Isoenzymes
  • LexA protein, Bacteria
  • Proto-Oncogene Proteins
  • Recombinant Fusion Proteins
  • prostate apoptosis response-4 protein
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-mos
  • Proto-Oncogene Proteins c-raf
  • Protein Kinase C
  • Serine Endopeptidases