Schematic Illustration of Glucosamine (GlcN) Effects on Granule Polarization in NK-92 Cells.

(A) A simplified scheme of the IL2-activated granule polarization. IL2 treatment of NK-92 cells induces a strong activation of AKT kinase and the PI3K pathway. PI3K indirectly phosphorylates ERK by forming a complex with IQGAP1, RAC, MEK, and ERK. Simultaneously, AKT kinase triggers phosphorylation of FOXO1, which is then translocated to the cytosol. In the cytosol, FOXO1 suppresses ERK phosphorylation by binding to IQGAP1, leading to transient phosphorylation of ERK. Paxillin is phosphorylated by ERK, and this phosphorylation regulates granule migration. (B) GlcN inhibits FOXO1 phosphorylation, resulting in its nuclear localization, which further promotes prolonged phosphorylation of ERK, resulting in translocation of ERK into the nucleus. Additionally, GlcN prevents phosphorylation of paxillin, leading to appearance of unpolarized granules and immunosuppression of NK-92 cells.