PIP4Ks Suppress Insulin Signaling through a Catalytic-Independent Mechanism.

ABSTRACT: Insulin stimulates the conversion of phosphatidylinositol-4,5-bisphosphate (PI(4,5)P₂) to phosphatidylinositol-3,4,5-trisphosphate (PI(3,4,5)P₃), which mediates downstream cellular responses. PI(4,5)P₂ is produced by phosphatidylinositol-4-phosphate 5-kinases (PIP5Ks) and by phosphatidylinositol-5-phosphate 4-kinases (PIP4Ks). Here, we show that the loss of PIP4Ks (PIP4K2A, PIP4K2B, and PIP4K2C) in vitro results in a paradoxical increase in PI(4,5)P₂ and a concomitant increase in insulin-stimulated production of PI(3,4,5)P₃. The reintroduction of either wild-type or kinase-dead mutants of the PIP4Ks restored cellular PI(4,5)P₂ levels and insulin stimulation of the PI3K pathway, suggesting a catalytic-independent role of PIP4

SUBMITTER: Wang DG 

PROVIDER: S-EPMC6619495 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature