Downregulation of glycogen synthase kinase-3beta (GSK-3beta) protein expression during neuroblastoma IMR-32 cell differentiation.
Glycogen synthase kinase-3gamma (GSK-3beta) is a multifunctional protein kinase that phosphorylates a variety of substrates including the neuronal-specific microtubule-associated protein tau. Here we report that the down-regulation of the GSK-3beta protein is an early event in the course of the differentiation of human neuroblastoma IMR-32 cells. This decline in GSK-3beta is accompanied by a significant decrease in the phosphorylation state of tau protein. A noteworthy increase in tau protein expression also takes place later during the differentiation of IMR-32 cells. The augmented expression and diminished phosphorylation of tau protein in differentiated IMR-32 cells can be correlated with increments in the assembly of microtubules and in the association of tau with microtubules. These results suggest a contribution of a decrease in GSK-3beta to molecular events leading to neuroblastoma cell differentiation. Among these, tau protein dephosphorylation might favor microtubule stabilization within neurites.
Muñoz-Montaño
J R
JR
Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, Spain.
Moreno
F J
FJ
Avila
J
J
Díaz-Nido
J
J
D003994:Bucladesine / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D015536:Down-Regulation; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D006801:Humans; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects; D016875:tau Proteins / Q000378:metabolism*
D016875:tau Proteins; D003994:Bucladesine; D038341:Glycogen Synthase Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3