PIP4K attenuates PIP5K lipid kinase activity by disrupting membrane-mediated dimerization.

ABSTRACT: The phosphatidylinositol 4-phosphate 5-kinase (PIP5K) family of enzymes generate most of the phosphatidylinositol-4,5-bisphosphate (PI(4,5)P₂) lipids in eukaryotes. In solution, PIP5K exists in a weak monomer-dimer equilibrium but undergoes membrane-mediated dimerization, which potentiates lipid kinase activity. In vivo, however, PI(4,5)P₂ levels are held remarkably constant due to the homeostatic regulation of PIP5K by PIP4K. We hypothesized that mechanisms that regulate PIP5K dimerization could function to buffer lipid kinase activity, thus providing a mechanism for maintaining relatively constant PI(4,5)P₂ levels at the plasma membrane. Due the transient nature and density dependence of PIP5K dimerization, deciphering how other proteins modulate PIP5K di

SUBMITTER: Duewell BR 

PROVIDER: S-EPMC12485675 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature