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

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.
Mesh Terms:
Alanine, Amino Acid Sequence, Animals, Aspartic Acid, Binding Sites, Carrier Proteins, Cloning, Molecular, Consensus Sequence, Fluorescent Antibody Technique, Indirect, Heat-Shock Proteins, Humans, Molecular Sequence Data, Mutagenesis, Site-Directed, Phosphorylation, Protein Kinase C, Rats, Recombinant Proteins, Saccharomyces cerevisiae, Schizosaccharomyces, Sequence Alignment, Transfection, Zinc Fingers
Proc. Natl. Acad. Sci. U.S.A.
Date: Jun. 10, 1997
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