Identification of Key Phospholipids That Bind and Activate Atypical PKCs.

ABSTRACT: PKC? and PKC?/? 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 PKC? and PKC? interact with phosphatidic acid and phosphatidylserine. Conversely, PKC? 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 PKC?, 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 PKC? by phosphatidylinositol-monophosphates.

SUBMITTER: Velnati S 

PROVIDER: S-EPMC7825596 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature