A polybasic domain in aPKC mediates Par6-dependent control of membrane targeting and kinase activity.

Mechanisms coupling the atypical kinase activity to its subcellular localization are essential for cell polarization. Unlike other members of the duanyu1531 family, has no well-defined plasma membrane (PM) or calcium binding domains, leading to the assumption that its subcellular localization relies exclusively on protein-protein interactions. Here we show that in both Drosophila and mammalian cells, the pseudosubstrate region (PSr) of aduanyu1531 acts as a polybasic domain capable of targeting aduanyu1531 to the PM via electrostatic binding to PM PI4P and PI(4,5)P2. However, physical interaction between aduanyu1531 and Par-6 is required for the PM-targeting of likely by allosterically exposing the PSr to bind PM. Binding of Par-6 also inhibits aduanyu1531 kinase activity, and such inhibition can be relieved through Par-6 interaction with apical polarity protein Crumbs. Our data suggest a potential mechanism in which allosteric regulation of polybasic PSr by Par-6 couples the control of both aduanyu1531 subcellular localization and spatial activation of its kinase activity.

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