Implication of cyclin-dependent kinases and glycogen synthase kinase 3 in the phosphorylation of microtubule-associated protein 1B in developing neuronal cells.
Phosphorylation at certain proline-directed sites on the microtubule-associated protein 1B (MAP1B) is a characteristic feature of mitotic neuronal precursor cells and developing neurons and is particularly abundant within growing axons. This mode of MAP1B phosphorylation disappears from mature neurons, except in those neurons that have a high regenerative potential, and is aberrantly up-regulated in degenerating neurons within the brains of Alzheimer's disease patients. Here, we report that this type of MAP1B phosphorylation is practically abolished in proliferating neuroblastoma cells that are treated with chemical inhibitors of cyclin-dependent kinases. In contrast, these drugs have no significant effect on MAP1B phosphorylation in either differentiated neuroblastoma cells or cerebellar granule neurons. Interestingly, lithium, which is a potent inhibitor of glycogen synthase kinase 3, suppresses this mode of MAP1B phosphorylation in differentiated neuroblastoma cells and cerebellar granule neurons. This is consistent with a major role of cyclin-dependent kinases in catalyzing this type of MAP1B phosphorylation in proliferating neural cells, whereas glycogen synthase kinase 3 would be largely responsible for this mode of MAP1B phosphorylation in postmitotic neurons that are extending axons. Both cyclin-dependent kinases and glycogen synthase kinase 3 might contribute to the aberrant MAP1B phosphorylation observed in Alzheimer's disease.
García-Pérez
J
J
Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, Spain.
Avila
J
J
Díaz-Nido
J
J
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009447:Neuroblastoma / Q000201:enzymology / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000201:enzymology* / Q000378:metabolism; D010766:Phosphorylation; D011392:Proline / Q000502:physiology; D051381:Rats; D014407:Tumor Cells, Cultured
D008869:Microtubule-Associated Proteins; C085284:microtubule-associated protein 1B; D011392:Proline; D038341:Glycogen Synthase Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D018844:Cyclin-Dependent Kinases; D038362:Glycogen Synthase Kinase 3