A mammalian PAR-3–PAR-6 complex implicated in Cdc42/Rac1 and aPKC signalling and cell polarity
Abstract
Cellular asymmetry is critical for the development of multicellular organisms. Here we show that homologues of proteins necessary for asymmetric cell division in Caenorhabditis elegans associate with each other in mammalian cells and tissues. mPAR-3 and mPAR-6 exhibit similar expression patterns and subcellular distributions in the CNS and associate through their PDZ (PSD-95/Dlg/ZO-1) domains. mPAR-6 binds to Cdc42/Rac1 GTPases, and mPAR-3 and mPAR-6 bind independently to atypical protein kinase C (aPKC) isoforms. In vitro, mPAR-3 acts as a substrate and an inhibitor of aPKC. We conclude that mPAR-3 and mPAR-6 have a scaffolding function, coordinating the activities of several signalling proteins that are implicated in mammalian cell polarity.
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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 Lin et al, 2000
Rac can bind to Par6 and thus potentially activate aPKC.
“It has been shown that Rac can bind to Par6 and thus potentially activate aPKC (Johansson 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 Lin et al, 2000
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- Authors
- Lin, D., Edwards, A. S., Fawcett, J. P., Mbamalu, G., Scott, J. D., & Pawson, T.
- Affiliations
- Mount Sinai Hospital (CA)
- Howard Hughes Medical Institute (US)
- Venue
- Nature Cell Biology
- Published
- 2000-07-17
- Volume
- 2
- Issue
- 8
- Pages
- 540-547
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W2171761187
- Cited by
- 743
- References
- 2
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 6 · 2023: 14 · 2022: 20 · 2021: 20 · 2020: 23 · 2019: 18 · 2018: 13 · 2017: 22 · 2016: 24 · 2015: 33 · 2014: 30 · 2013: 36 · 2012: 26
- FWCI
- 14.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (P01DK044239, DK44239)
- 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
- Par3, Par6, Cdc42, Rac1, atypical protein kinase C, cell polarity, asymmetric cell division, PDZ domain, protein scaffolding, mammalian cells
- MeSH terms
- Animals, Brain, Cell Fractionation, Cell Line, Cloning, Molecular, Enzyme Activation, Immunohistochemistry, Mutation, Phosphorylation, Precipitin Tests, Protein Binding, Protein Kinase C, Proteins, Recombinant Fusion Proteins, Transfection, Signal Transduction, Helminth Proteins, Cell Polarity, Protein Serine-Threonine Kinases, Protein Structure, Tertiary, Protein Isoforms, cdc42 GTP-Binding Protein, Amino Acid Motifs, rac1 GTP-Binding Protein, Caenorhabditis elegans Proteins, Macromolecular Substances, Mice
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