Figure 1.

Neural crest development. Neural crest cells are induced at the border of the neural plate. On induction, premigratory neural crest must delaminate and undergo an EMT from the neuroepithelium becoming fully mesenchymal. Migratory neural crest cells then move to their final destinations where they differentiate into a variety of cell types. Our work suggests that ALK acts in the premigratory neural crest to phosphorylate GSK3 at tyrosine 279 on GSK3α and tyrosine 216 on GSK3β. This serves to activate GSK3 in the cells undergoing EMT. GSK3 is proposed to regulate a signaling cascade controlling lamellipodial dynamics at the leading edge of the migratory front. In neuroblastoma cells, ALK activation correlates with high levels of phospho-tyrosine GSK3; this may maintain the migratory and proliferative capacity of the neuroblastoma cells while preventing differentiation. ALK indicates anaplastic lymphoma kinase; EMT, epithelial-mesenchymal transition; GSK3, glycogen synthase kinase 3.