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bioRxiv · 10.1101/588624

A Polybasic Domain in aPKC Mediates Par-6-Dependent Control of Plasma Membrane Targeting and Kinase Activity

Hong, Y.·Dong, W.·Lu, J.·Zhang, X.·Wu, Y.·Lettieri, K.·Hammond, G.
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Abstract

Mechanisms coupling the atypical PKC (aPKC) kinase activity to its subcellular localization are essential for cell polarization. Unlike other members of the PKC family, aPKC 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 aPKC acts as a polybasic domain capable of targeting aPKC to the PM via electrostatic binding to PM PI4P and PI(4,5)P2. However, physical interaction between aPKC and Par-6 is required for the PM-targeting of aPKC, likely by allosterically exposing the PSr to bind PM. Binding of Par-6 also inhibits aPKC 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 aPKC subcellular localization and spatial activation of its kinase activity. eTOC SummaryDong et al. discover that the pseudo-substrate region (PSr) in aPKC is a polybasic domain capable of electrostatically targeting aPKC to plasma membrane. Allosteric regulation of PSr by Par-6 couples the control of both aPKC subcellular localization and spatial activation of kinase activity.

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Hong, Y., Dong, W., Lu, J., Zhang, X., Wu, Y., Lettieri, K., Hammond, G.. 2019-03-26. A Polybasic Domain in aPKC Mediates Par-6-Dependent Control of Plasma Membrane Targeting and Kinase Activity. https://doi.org/10.1101/588624

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