Kinase Alpha 2 Acts as a Protein Kinase to Promote Lipolysis of Lipid Droplets

However, the mechanism underlying the initiation of lipid droplet lipolysis is not well understood. We demonstrate here that glucose deprivation induces the binding of choline kinase (CHK)2 to lipid droplets, which is sequentially mediated by AMPK-dependent CHK2 S279 phosphorylation and KAT5-dependent CHK2 K247 acetylation.

Importantly, CHK2 with altered catalytic domain conformation functions as a protein kinase and phosphorylates PLIN2 at Y232 and PLIN3 at Y251. The phosphorylated PLIN2/3 dissociate from lipid droplets and are degraded by Hsc70-mediated autophagy, thereby promoting lipid droplet lipolysis, fatty acid oxidation, and brain tumor growth. In addition, the levels of CHK2 S279 phosphorylation, CHK2 K247 acetylation, and PLIN2/3 phosphorylation are positively correlated with each other in human glioblastoma specimens and are associated with poor prognosis in glioblastoma patients.