Increase of the target inhibition effects on FLT3 based on the glycosylation and cellular localization status

我们发现，糖基化机制的抑制降低了野生型Flt3的细胞表面表达，并通过抑制野生型Flt3表达细胞中激活的STATs而诱导了细胞死亡，而在表达突变的Flt3细胞中则没有。我们证明，在野生型Flt3中，糖基化是通过FL刺激自动磷酸化所必需的，而突变的Flt3在糖基化之前在细胞质内被自动磷酸化，从而通过STATS磷酸化导致细胞增殖。

We identified that the inhibition of glycosylation machinery reduced the cell surface expression of wild type FLT3 and induced cell death through the inhibition of activated STATs in wild type FLT3-expressing cells, but not in mutant FLT3-expressing cells. We demonstrated that the glycosylation is essential for auto-phosphorylation via FL-stimulation in wild type FLT3, and that mutant FLT3 is auto-phosphorylated within the cytoplasm before the glycosylation resulting in the cell proliferation via STATs phosphorylations.