mTORC2 Protein-mediated Protein Kinase B (Akt) Serine 473 Phosphorylation Is Not Required for Akt1 Activity in Human Platelets

• DOI: 10.1074/jbc.m110.202341
• Publication Date: 2011-05-19T00:18:18Z
• Authors: Samantha F. Moore; Roger W. Hunter; Ingeborg Hers
• Keywords: mTORC2; AKT2

Protein kinase B (PKB, Akt) is a Ser/Thr involved in the regulation of cell survival, proliferation, and metabolism activated by dual phosphorylation on Thr308 activation loop Ser473 hydrophobic motif. It plays contributory role to platelet function, although little known about its regulation. In this study, we investigated mammalian target rapamycin complex (mTORC)-2 Akt using recently identified small molecule ATP competitive mTOR inhibitors PP242 Torin1. Both Torin1 blocked thrombin insulin-like growth factor 1-mediated with an IC50 between 1 5 nm, whereas mTORC1 inhibitor had no effect. Interestingly, effect phosphorylation, Akt1 activity, substrate glycogen synthase 3β, indicating that not necessary for maximal activity. contrast, Akt2 activity was significantly reduced, concurrent inhibition PRAS40 presence Other signaling pathways, including phospholipase C/PKC MAPK pathway, were unaffected Together, these results demonstrate mTORC2 phosphorylates human platelets but dispensable