Interaction of protein kinase C zeta with ZIP, a novel protein kinase C-binding protein

Proc Natl Acad Sci U S A. 1997 Jun 10;94(12):6191-6. doi: 10.1073/pnas.94.12.6191.


The atypical protein kinase C (PKC) member PKC-zeta has been implicated in several signal transduction pathways regulating differentiation, proliferation or apoptosis of mammalian cells. We report here the identification of a cytoplasmic and membrane-associated protein that we name zeta-interacting protein (ZIP) and that interacts with the regulatory domain of PKC-zeta but not classic PKCs. The structural motifs in ZIP include a recently defined ZZ zinc finger as a potential protein binding module, two PEST sequences and a novel putative protein binding motif with the consensus sequence YXDEDX5SDEE/D. ZIP binds to the pseudosubstrate region in the regulatory domain of PKC-zeta and is phosphorylated by PKC-zeta in vitro. ZIP dimerizes via the same region that promotes binding to PKC-zeta suggesting a competitive situation between ZIP:ZIP and ZIP:PKC-zeta complexes. In the absence of PKC-zeta proper subcellular localization of ZIP is impaired and we show that intracellular targeting of ZIP is dependent on a balanced interaction with PKC-zeta. Taking into account the recent isolation of ZIP by others in different contexts we propose that ZIP may function as a scaffold protein linking PKC-zeta to protein tyrosine kinases and cytokine receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine
  • Amino Acid Sequence
  • Animals
  • Aspartic Acid
  • Binding Sites
  • Carrier Proteins / biosynthesis
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism*
  • Cloning, Molecular
  • Consensus Sequence
  • Fluorescent Antibody Technique, Indirect
  • Heat-Shock Proteins
  • Humans
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Phosphorylation
  • Protein Kinase C / biosynthesis
  • Protein Kinase C / chemistry
  • Protein Kinase C / metabolism*
  • Rats
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae / metabolism
  • Schizosaccharomyces / metabolism
  • Sequence Alignment
  • Sequestosome-1 Protein
  • Transfection
  • Zinc Fingers


  • Carrier Proteins
  • Heat-Shock Proteins
  • Recombinant Proteins
  • Sequestosome-1 Protein
  • Sqstm1 protein, rat
  • Aspartic Acid
  • protein kinase C zeta
  • Protein Kinase C
  • Alanine

Associated data

  • GENBANK/Y08355