Identification of Key Phospholipids That Bind and Activate Atypical PKCs

Overview

Journal Biomedicines

Specialty Biomedical Engineering

Date 2021 Jan 9

PMID 33419210

Citations 6

Authors

Suresh Velnati

Sara Centonze

Federico Girivetto

Daniela Capello

Ricardo M Biondi

Alessandra Bertoni

Roberto Cantello

Beatrice Ragnoli

Mario Malerba

Andrea Graziani

Gianluca Baldanzi

Affiliations

Soon will be listed here.

Abstract

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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