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

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

^*Max-Delbrück-Laboratorium in der Max-Planck-Gesellschaft, Carl-von-Linné-Weg 10, D-50829 Cologne, Germany; and ^‡Institut für Entwicklungsbiologie, Universität zu Köln, Gyrhofstrasse 17, D-50923 Cologne, Germany

Abstract

The atypical protein kinase C (PKC) member PKC-ζ 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-ζ 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 YXDEDX₅ SDEE/D. ZIP binds to the pseudosubstrate region in the regulatory domain of PKC-ζ and is phosphorylated by PKC-ζ in vitro. ZIP dimerizes via the same region that promotes binding to PKC-ζ suggesting a competitive situation between ZIP:ZIP and ZIP:PKC-ζ complexes. In the absence of PKC-ζ proper subcellular localization of ZIP is impaired and we show that intracellular targeting of ZIP is dependent on a balanced interaction with PKC-ζ. 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-ζ to protein tyrosine kinases and cytokine receptors.

Footnotes

↵ † To whom reprint requests should be sent at present address: Laboratory for Molecular Cell Biology, University College, London, Medical Research Council, Gordon Street, London WC1E 6BT, U.K.
Susan S. Taylor, University of California at San Diego, La Jolla, CA
Data deposition: The sequence reported in this paper has been deposited in the GenBank database (accession no. Y08355Y08355).
ABBREVIATIONS:

PKC,

protein kinase C;

GST,

glutathione S-transferase;

ZIP,

PKC-ζ-interacting protein;

ERK,

extracellular signal-regulated kinase;

MEK,

MAPK kinase ERK kinase