Mannose‐6‐phosphate stimulates proliferation of neuronal precursor cells

Abstract
The mitogenic signal function of mannose‐6‐phosphate (Man‐6‐P)/insulin‐like growth factor II (IGF‐II) receptors was studied in neuronal precursor cells from developing rat brain (E15). About 30% of the cellular Man‐6‐P/IGF‐II receptors were present on the cell surface. Man‐6‐P and IGF‐II stimulated DNA synthesis twofold and their effects were additive. Antibody 3637 to the Man‐6‐P/IGF‐II receptor blocked the response to Man‐6‐P but not that to IGF‐II. Other phosphorylated hexoses were also active. Fructose‐1‐phosphate was equally potent with Man‐6‐P, whereas glucose‐6‐phosphate was 5 times less potent. We conclude that Man‐6‐P‐containing proteins and IGF‐II act as mitogens in developing brain by interaction with the Man‐6‐P/IGF‐II receptor and the IGF‐I receptor, respectively.