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aPKC Inhibition by Par3 CR3 Flanking Regions Controls Substrate Access and Underpins Apical-Junctional Polarization

DOI: 10.1016/j.devcel.2016.07.018 DOI Help

Authors: Erika V. Soriano (The Francis Crick Institute) , Marina E. Ivanova (The Francis Crick Institute) , Georgina Fletcher (The Francis Crick Institute) , Philippe Riou (The Francis Crick Institute) , Phillip P. Knowles (The Francis Crick Institute) , Karin Barnouin (The Francis Crick Institute) , Andrew Purkiss (The Francis Crick Institute) , Brenda Kostelecky (The Francis Crick Institute) , Peter Saiu (The Francis Crick Institute) , Mark Linch (The Francis Crick Institute) , Ahmed Elbediwy (The Francis Crick Institute) , Svend Kjær (The Francis Crick Institute) , Nicola O’reilly (The Francis Crick Institute) , Ambrosius p. Snijders (The Francis Crick Institute) , Peter j. Parker (The Francis Crick Institute; King's College London) , Barry j. Thompson (The Francis Crick Institute) , Neil q. Mcdonald (The Francis Crick Institute; Birkbeck College)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Developmental Cell , VOL 38 , PAGES 384 - 398

State: Published (Approved)
Published: August 2016
Diamond Proposal Number(s): 8015 , 9826 , 13775

Open Access Open Access

Abstract: Atypical protein kinase C (aPKC) is a key apical-basal polarity determinant and Par complex component. It is recruited by Par3/Baz (Bazooka in Drosophila) into epithelial apical domains through high-affinity interaction. Paradoxically, aPKC also phosphorylates Par3/Baz, provoking its relocalization to adherens junctions (AJs). We show that Par3 conserved region 3 (CR3) forms a tight inhibitory complex with a primed aPKC kinase domain, blocking substrate access. A CR3 motif flanking its PKC consensus site disrupts the aPKC kinase N lobe, separating P-loop/αB/αC contacts. A second CR3 motif provides a high-affinity anchor. Mutation of either motif switches CR3 to an efficient in vitro substrate by exposing its phospho-acceptor site. In vivo, mutation of either CR3 motif alters Par3/Baz localization from apical to AJs. Our results reveal how Par3/Baz CR3 can antagonize aPKC in stable apical Par complexes and suggests that modulation of CR3 inhibitory arms or opposing aPKC pockets would perturb the interaction, promoting Par3/Baz phosphorylation.

Subject Areas: Biology and Bio-materials


Instruments: I02-Macromolecular Crystallography , I03-Macromolecular Crystallography , I04-Macromolecular Crystallography , I24-Microfocus Macromolecular Crystallography

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