PTEN-regulated signaling pathway

PTEN-regulated signaling pathway. In response to receptor tyrosine kinase activation, PI3K phosphorylates and converts the lipid second messenger phosphatidylinositol (4,5) bisphosphate (PIP2) into phosphatidylinositol (3,4,5) trisphosphate (PIP3), which recruits and activates phosphatidylinositol-dependent kinase 1/2 (PDK1/2). PDK1/2, in turn, phosphorylates and activates Akt. PTEN catalyzes the conversion from PIP3 to PIP2. Thus, inactivation of PTEN results in the accumulation of PIP3 and the activation of Akt. Akt controls a host of signaling molecules, including GSK-3 and TSC1/2. Inactivation of the TSC1/2 complex leads to activation of mTOR, which integrates various cellular signals including nutrient availability to control protein translation, cell growth, and other processes. The ribosomal protein S6 kinase (RP-S6) and the eukaryotic initiation factor 4E (eIF-4E) binding protein 1 (4E-BP1) are the mTOR effector molecules executing these functions. Cellular stresses such as hypoxia and low energy induce expression of Redd1/2, which augments TSC1/2 activity and in turn suppress the mTOR activity.

Publication

Neuronal intrinsic barriers for axon regeneration in the adult CNS. () Fang Sun, et al. Curr Opin Neurobiol. ;20(4):510-518. Figure: F3. All organisms Drosophila melanogaster Homo sapiens

Disease mentions