Identification of key phospholipids that bind and activate atypical PKCs

  • PKCζ and PKCι/λ form the atypical protein kinase C subgroup, characterised by a lack of regulation by calcium and the neutral lipid diacylglycerol. To better understand the regulation of these kinases, we systematically explored their interactions with various purified phospholipids using the lipid overlay assays, followed by kinase activity assays to evaluate the lipid effects on their enzymatic activity. We observed that both PKCζ and PKCι interact with phosphatidic acid and phosphatidylserine. Conversely, PKCι is unique in binding also to phosphatidylinositol-monophosphates (e.g., phosphatidylinositol 3-phosphate, 4-phosphate, and 5-phosphate). Moreover, we observed that phosphatidylinositol 4-phosphate specifically activates PKCι, while both isoforms are responsive to phosphatidic acid and phosphatidylserine. Overall, our results suggest that atypical Protein kinase C (PKC) localisation and activity are regulated by membrane lipids distinct from those involved in conventional PKCs and unveil a specific regulation of PKCι by phosphatidylinositol-monophosphates.

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Author:Suresh Velnati, Sara Centonze, Federico Girivetto, Daniela Capello, Ricardo M. Biondi, Alessandra Bertoni, Roberto Cantello, Beatrice Ragnoli, Mario Malerba, Andrea Graziani, Gianluca Baldanzi
Parent Title (English):Biomedicines
Place of publication:Basel
Document Type:Article
Date of Publication (online):2021/01/06
Date of first Publication:2021/01/06
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2021/01/07
Tag:kinase regulation; lipid signalling; lipid-protein interaction; membrane; phosphatidylinositols
Issue:Article 45
Page Number:17
Institutes:Medizin / Medizin
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0