AKT2
AKT2 is the second of the three AKT isoforms, distinguished by its dominant role in insulin-stimulated glucose metabolism.
Function
AKT2 shares the activation mechanism of AKT1 — membrane recruitment by PI3K-generated PIP3, phosphorylation by PDK1 and mTORC2 — and much of its substrate set, but its tissue distribution and knockout phenotype mark it as the insulin-response isoform. AKT2 knockout mice are insulin-resistant and diabetic, while AKT1 knockouts show growth defects; the two isoforms phosphorylate overlapping substrates with different efficiencies, and AKT2 dominates the GLUT4 trafficking route that moves glucose transporters to the muscle and fat cell membrane after a meal.
In cancer
AKT2 is amplified in a substantial fraction of ovarian, breast, and pancreatic cancers — the amplicon at 19q13 containing AKT2 was among the first AKT amplifications found in human tumors. As with AKT1, hyperactivation more often arrives indirectly through PIK3CA mutation or PTEN loss, and isoform-specific inhibitors remain an open pharmacology problem because the three AKTs overlap heavily in substrate specificity.
Notes
- Human gene symbol: AKT2; UniProt P31751; 481 amino acids; AGC kinase family.