AKT/GSK3 signaling pathway and schizophrenia - PubMed (original) (raw)

The AKT signaling pathway. AKT is activated by PI3K, which itself is activated by several upstream signaling pathways such as insulin receptors, receptor tyrosine kinases, G protein coupled receptors, cytokine receptors, etc. After activation, it targets several downstream molecules and change their activity by phosphorylation or complex formation. AKT is involved in cell proliferation, glucose metabolism, cell survival, cell cycle, protein synthesis, and in neuronal morphology and plasticity by regulation of several downstream molecules shown in this figure. AKT is involved in cell proliferation through interaction with a number of proteins involved in cell cycle, including Cyclin D1, p21Cip, p27Kip, Myt1, and Wee1. AKT also plays a crucial role in cell survival through interaction with Bad, MDM2 and the subsequent regulation of p53, FoxO1, Bcl-2, and Bax. AKT regulates glucose metabolism through regulation of GSK-3, PFKFB2, PIP5K, and AS160. It could also affect protein synthesis through interaction with S6 kinase, TSC1, and mTOR signaling. In more recent years, AKT's role in neurodegeneration was uncovered, mediated through phosphorylation of Huntingtin and Ataxin-1. AKT also has a role in synaptic plasticity, by phosphorylation of GABAA receptor. Pathway diagram reproduced courtesy of Cell Signaling Technology, Inc. (