The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42
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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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).”
From E‐cadherin is essential for in vivo epidermal barrier function by regulating tight junctions (2005) · cites this paper as Joberty 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
- Licence
- www.springer.com/tdm (tdm)
- 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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