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PMID: 10934475 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A mammalian PAR-3-PAR-6 complex implicated in Cdc42/Rac1 and aPKC signalling and cell polarity.

Nature cell biology ·Vol. 2 ·No. 8 ·2000-08-00 ·Pages 540-7

Lin D, Edwards AS, Fawcett JP, Mbamalu G, Scott JD, Pawson T

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.

MeSH Terms

Amino Acid Motifs Animals Brain/metabolism Caenorhabditis elegans Proteins Cell Fractionation Cell Line Cell Polarity Cloning, Molecular Enzyme Activation Helminth Proteins/chemistry,genetics,metabolism Immunohistochemistry Macromolecular Substances Mice Mutation Phosphorylation Precipitin Tests Protein Binding Protein Isoforms/antagonists & inhibitors,chemistry,metabolism Protein Kinase C/antagonists & inhibitors,chemistry,metabolism Protein Serine-Threonine Kinases Protein Structure, Tertiary Proteins/chemistry,genetics,metabolism Recombinant Fusion Proteins/chemistry,metabolism Signal Transduction Transfection cdc42 GTP-Binding Protein/chemistry,genetics,metabolism rac1 GTP-Binding Protein/chemistry,metabolism

Chemicals

Caenorhabditis elegans Proteins Helminth Proteins Macromolecular Substances Protein Isoforms Proteins Recombinant Fusion Proteins par-6 protein, C elegans PAR-3 protein, C elegans Protein Serine-Threonine Kinases PKC-3 protein Protein Kinase C cdc42 GTP-Binding Protein rac1 GTP-Binding Protein

Authors & Affiliations

6 authors, click to expand affiliations / ORCID

Lin D

Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada.

Edwards A S

Fawcett J P

Mbamalu G

Scott J D

Pawson T

Article Info

Journal

Nature cell biology

Abbr.

Nat Cell Biol

ISSN

1465-7392

DOI

10.1038/35019582

Published

2000-08-00

Pages

540-7

Language

English

Region

England

NLM ID

100890575

Subset

Grants

NIDDK NIH HHS · DK44239 · United States

Corrections

CommentIn

PMID: 10934484

External Links

PubMed source DOI: 10.1038/35019582 View journal details

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A mammalian PAR-3-PAR-6 complex implicated in Cdc42/Rac1 and aPKC signalling and cell polarity.

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