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

作者：Soriano Erika V; Ivanova Marina E; Fletcher Georgina; Riou Philippe; Knowles Philip P; Barnouin Karin; Purkiss Andrew; Kostelecky Brenda; Saiu Peter; Linch Mark; Elbediwy Ahmed; Kjaer Svend; O'Reilly Nicola; Snijders Ambrosius P; Parker Peter J; Thompson Barry J^*; McDonald Neil Q^*

来源：Developmental Cell, 2016, 38(4): 384-398.

DOI：10.1016/j.devcel.2016.07.018

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/alpha B/alpha C 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.

• 出版日期2016-8-22