Phosphatidylinositol 3-kinase (PI3K) has numerous cellular functions, including cell survival and proliferation. In this study, we demonstrated that the expression of the active form of PI3K induced dorsal differentiation and axis duplication and strongly induced the expression of neural markers. In contrast, the inhibition of PI3K activity by its dominant negative mutant induced the phenotype of losing posterior structures and the expression of ventral markers. Akt is an essential target of PI3K for neurogenesis. The expression of the active form of Akt induced axis duplication and increased the expression of neural markers. Inhibition of the Akt activity abolished the PI3K-induced double heads and axes. This signal transmits through its target, glycogen synthase kinase 3, which is known to mediate Wnt signaling for Xenopus development. These results identify a new function of PI3K/Akt signaling in axis formation and neurogenesis during Xenopus embryonic development and provide a direct link between growth factor-mediated PI3K/Akt signaling and Wnt signaling during embryonic development.
Phosphatidylinositol 3-kinase (PI3K)1 is a heterodimeric enzyme composed of a 110-kDa catalytic and an 85-kDa regulatory subunit (1). PI3K phosphorylates the D3 hydroxyl of phosphoinositides and produces phosphatidyl-inositol-3-phosphates. PI3K is activated by several receptor and nonreceptor protein tyrosine kinases (2, 3). The best known downstream target of PI3K is the serine-threonine kinase Akt, which transmits survival signals from growth factors (4, 5). Activation of Akt requires the following two factors: (i) the binding of the lipid second messengers to its intact pleckstrin homology domain; and (ii) the phosphorylation of the pleckstrin homology domain by the phosphoinositide-dependent kinase (6,
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