Mutations of FLT3 receptor affect its surface glycosylation, intracellular localization, and downstream signaling

摘要

This review describes the effects of FLT3 mutations that alter its intracellular localization and modify its glycosylation, leading to differences in downstream signaling pathways. The most common type of FLT3 mutation, internal tandem duplication (FLT3-ITD), leads to localization in the endoplasmic reticulum and constitutive strong activation of STAT5. In contrast, the ligand-activated FLT3-wild type is mainly expressed on the cell surface and activates MAP kinases. Based on these backgrounds, several reports have demonstrated that glycosylation inhibitors are effective for inhibition of FLT3-ITD expression and intracellular localization. The general subcellular localization regulatory mechanisms for receptor tyrosine kinases are also discussed.