Cargando…

p32 is a novel mammalian Lgl binding protein that enhances the activity of protein kinase Cζ and regulates cell polarity

Lgl (lethal giant larvae) plays an important role in cell polarity. Atypical protein kinase C (aPKC) binds to and phosphorylates Lgl, and the phosphorylation negatively regulates Lgl activity. In this study, we identify p32 as a novel Lgl binding protein that directly binds to a domain on mammalian...

Descripción completa

Detalles Bibliográficos
Autores principales: Bialucha, Carl U., Ferber, Emma C., Pichaud, Franck, Peak-Chew, Sew Y., Fujita, Yasuyuki
Formato: Texto
Lenguaje:English
Publicado: Rockefeller University Press|1 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064465/
https://www.ncbi.nlm.nih.gov/pubmed/17682048
http://dx.doi.org/10.1083/jcb.200612022
_version_ 1782137544287191040
author Bialucha, Carl U.
Ferber, Emma C.
Pichaud, Franck
Peak-Chew, Sew Y.
Fujita, Yasuyuki
author_facet Bialucha, Carl U.
Ferber, Emma C.
Pichaud, Franck
Peak-Chew, Sew Y.
Fujita, Yasuyuki
author_sort Bialucha, Carl U.
collection PubMed
description Lgl (lethal giant larvae) plays an important role in cell polarity. Atypical protein kinase C (aPKC) binds to and phosphorylates Lgl, and the phosphorylation negatively regulates Lgl activity. In this study, we identify p32 as a novel Lgl binding protein that directly binds to a domain on mammalian Lgl2 (mLgl2), which contains the aPKC phosphorylation site. p32 also binds to PKCζ, and the three proteins form a transient ternary complex. When p32 is bound, PKCζ is stimulated to phosphorylate mLgl2 more efficiently. p32 overexpression in Madin–Darby canine kidney cells cultured in a 3D matrix induces an expansion of the actin-enriched apical membrane domain and disrupts cell polarity. Addition of PKCζ inhibitor blocks apical actin accumulation, which is rescued by p32 overexpression. p32 knockdown by short hairpin RNA also induces cell polarity defects. Collectively, our data indicate that p32 is a novel regulator of cell polarity that forms a complex with mLgl2 and aPKC and enhances aPKC activity.
format Text
id pubmed-2064465
institution National Center for Biotechnology Information
language English
publishDate 2007
publisher Rockefeller University Press|1
record_format MEDLINE/PubMed
spelling pubmed-20644652008-02-13 p32 is a novel mammalian Lgl binding protein that enhances the activity of protein kinase Cζ and regulates cell polarity Bialucha, Carl U. Ferber, Emma C. Pichaud, Franck Peak-Chew, Sew Y. Fujita, Yasuyuki J Cell Biol Research Articles Lgl (lethal giant larvae) plays an important role in cell polarity. Atypical protein kinase C (aPKC) binds to and phosphorylates Lgl, and the phosphorylation negatively regulates Lgl activity. In this study, we identify p32 as a novel Lgl binding protein that directly binds to a domain on mammalian Lgl2 (mLgl2), which contains the aPKC phosphorylation site. p32 also binds to PKCζ, and the three proteins form a transient ternary complex. When p32 is bound, PKCζ is stimulated to phosphorylate mLgl2 more efficiently. p32 overexpression in Madin–Darby canine kidney cells cultured in a 3D matrix induces an expansion of the actin-enriched apical membrane domain and disrupts cell polarity. Addition of PKCζ inhibitor blocks apical actin accumulation, which is rescued by p32 overexpression. p32 knockdown by short hairpin RNA also induces cell polarity defects. Collectively, our data indicate that p32 is a novel regulator of cell polarity that forms a complex with mLgl2 and aPKC and enhances aPKC activity. Rockefeller University Press|1 2007-08-13 /pmc/articles/PMC2064465/ /pubmed/17682048 http://dx.doi.org/10.1083/jcb.200612022 Text en Copyright © 2007, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Bialucha, Carl U.
Ferber, Emma C.
Pichaud, Franck
Peak-Chew, Sew Y.
Fujita, Yasuyuki
p32 is a novel mammalian Lgl binding protein that enhances the activity of protein kinase Cζ and regulates cell polarity
title p32 is a novel mammalian Lgl binding protein that enhances the activity of protein kinase Cζ and regulates cell polarity
title_full p32 is a novel mammalian Lgl binding protein that enhances the activity of protein kinase Cζ and regulates cell polarity
title_fullStr p32 is a novel mammalian Lgl binding protein that enhances the activity of protein kinase Cζ and regulates cell polarity
title_full_unstemmed p32 is a novel mammalian Lgl binding protein that enhances the activity of protein kinase Cζ and regulates cell polarity
title_short p32 is a novel mammalian Lgl binding protein that enhances the activity of protein kinase Cζ and regulates cell polarity
title_sort p32 is a novel mammalian lgl binding protein that enhances the activity of protein kinase cζ and regulates cell polarity
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064465/
https://www.ncbi.nlm.nih.gov/pubmed/17682048
http://dx.doi.org/10.1083/jcb.200612022
work_keys_str_mv AT bialuchacarlu p32isanovelmammalianlglbindingproteinthatenhancestheactivityofproteinkinaseczandregulatescellpolarity
AT ferberemmac p32isanovelmammalianlglbindingproteinthatenhancestheactivityofproteinkinaseczandregulatescellpolarity
AT pichaudfranck p32isanovelmammalianlglbindingproteinthatenhancestheactivityofproteinkinaseczandregulatescellpolarity
AT peakchewsewy p32isanovelmammalianlglbindingproteinthatenhancestheactivityofproteinkinaseczandregulatescellpolarity
AT fujitayasuyuki p32isanovelmammalianlglbindingproteinthatenhancestheactivityofproteinkinaseczandregulatescellpolarity