Cited by 928Protein Kinase Regulation and GTPase SignalingDevelopmental Biology and Gene RegulationCellular Mechanics and Interactions

The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42

Joberty, Gérard, Petersen, Clark, Gao, Lin, Macara, Ian G.·2000·Nature Cell Biology

Abstract

PAR (partitioning-defective) proteins, which were first identified in the nematode Caenorhabditis elegans, are essential for asymmetric cell division and polarized growth, whereas Cdc42 mediates establishment of cell polarity. Here we describe an unexpected link between these two systems. We have identified a family of mammalian Par6 proteins that are similar to the C. elegans PDZ-domain protein PAR-6. Par6 forms a complex with Cdc42-GTP, with a human homologue of the multi-PDZ protein PAR-3 and with the regulatory domains of atypical protein kinase C (PKC) proteins. This assembly is implicated in the formation of normal tight junctions at epithelial cell-cell contacts. Thus, Par6 is a key adaptor that links Cdc42 and atypical PKCs to Par3.

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Crossref · 10.1038/35019573

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  • Activation of the Par3/Par6/aPKC complex is achieved by binding to Cdc42, resulting in phosphorylation and activation of aPKC.

    “Activation of the Par3/Par6/aPKC complex is achieved by binding to the small GTPase Cdc42, resulting in the phosphorylation and activation of aPKC (Joberty et al, 2000;Lin et al, 2000).”

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References 38 · Cited by 928

Authors
Joberty, G., Petersen, C., Gao, L., & Macara, I. G.
Affiliations
University of Virginia (US)
Venue
Nature Cell Biology
Published
2000-07-17
Volume
2
Issue
8
Pages
531-539
ISSN
  • 1465-7392 (ISSN-L)
  • 1476-4679
OpenAlex
W1560056935
Cited by
928
References
38
Citations by year
2026: 8 · 2025: 9 · 2024: 10 · 2023: 16 · 2022: 21 · 2021: 31 · 2020: 31 · 2019: 34 · 2018: 23 · 2017: 30 · 2016: 23 · 2015: 34 · 2014: 41 · 2013: 47 · 2012: 57
FWCI
17.46
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Cell Biology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01ca038888-17)
  • National Cancer Institute (P01 CA 40042, R01 CA-38888, P01CA040042)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
Keywords
Par6, Par3, atypical protein kinase C, Cdc42, cell polarity, asymmetric cell division, tight junctions, PDZ domain, adaptor proteins, PAR proteins
MeSH terms
Amino Acid Sequence, Animals, Cell Line, Dogs, Epithelial Cells, Fluorescent Antibody Technique, Guanosine Triphosphate, Humans, Isoenzymes, Membrane Proteins, Molecular Sequence Data, Phosphoproteins, Protein Binding, Protein Kinase C, Proteins, RNA, Messenger, Substrate Specificity, Helminth Proteins, Sequence Alignment, Cell Polarity, Protein Serine-Threonine Kinases, Protein Structure, Tertiary, Tight Junctions, rho GTP-Binding Proteins, cdc42 GTP-Binding Protein, Two-Hybrid System Techniques, Caenorhabditis elegans Proteins, Macromolecular Substances, Adaptor Proteins, Signal Transducing, Mice, Zonula Occludens-1 Protein

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