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J. Cell Biol.,
Volume 143, Number 1, October 5, 1998 95-106


* Department of Molecular Biology and Cell polarity is fundamental to differentiation and function of most cells. Studies in mammalian
epithelial cells have revealed that the establishment
and maintenance of cell polarity depends upon cell adhesion, signaling networks, the cytoskeleton, and protein transport. Atypical protein kinase C (PKC) isotypes PKC
Department of Pathology, Yokohama City University School of Medicine, Yokohama
236-0004, Japan; § Department of Anatomy and Cell Biology, Gunma University School of Medicine, Maebashi 371-8511, Japan;
Fundamental Research Laboratories, NEC Corporation, Tsukuba 305-0841, Japan; and ¶ Section of Genetics and Development,
101 Biotechnology Building, Cornell University, Ithaca, New York 14853
and PKC
have been implicated in
signaling through lipid metabolites including phosphatidylinositol 3-phosphates, but their physiological role remains elusive. In the present study we report the
identification of a protein, ASIP (atypical PKC isotype-specific interacting protein), that binds to aPKCs,
and show that it colocalizes with PKC
to the cell junctional complex in cultured epithelial MDCKII cells and
rat intestinal epithelia. In addition, immunoelectron microscopy revealed that ASIP localizes to tight junctions in intestinal epithelial cells. Furthermore, ASIP
shows significant sequence similarity to Caenorhabditis
elegans PAR-3. PAR-3 protein is localized to the anterior periphery of the one-cell embryo, and is required
for the establishment of cell polarity in early embryos.
ASIP and PAR-3 share three PDZ domains, and can
both bind to aPKCs. Taken together, our results suggest a role for a protein complex containing ASIP and
aPKC in the establishment and/or maintenance of epithelial cell polarity. The evolutionary conservation of
the protein complex and its asymmetric distribution in
polarized cells from worm embryo to mammalian-differentiated cells may mean that the complex functions
generally in the organization of cellular asymmetry.
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