Nature Cell Biology
2, 540 - 547 (2000)
Published online: 17 July 2000; | doi:10.1038/35019582
A mammalian PAR-3−PAR-6 complex implicated in Cdc42/Rac1 and aPKC
signalling and cell polarityDan Lin1, 2, Amelia S. Edwards3, James P. Fawcett1, Geraldine Mbamalu1, John D. Scott3
& Tony Pawson1, 21
Program in Molecular Biology and Cancer, Samuel Lunenfeld
Research Institute, Mount Sinai Hospital, 600 University Avenue
, Toronto, Ontario M5G 1X5,
Canada
pawson@mshri.on.ca
2
Department of Molecular and Medical Genetics, University
of Toronto, Toronto, Ontario M5S 1A8,
Canada
3
Howard Hughes Medical Institute, Vollum Institute,
L474, Oregon Health Sciences University, 3181 Southwest Sam
Jackson Park Road, Portland, Oregon 97201
, USA
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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