Journal
ELIFE
Volume 3, Issue -, Pages -Publisher
ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.03751
Keywords
-
Categories
Funding
- National Institutes of Health [1R01NS080944-01, U54CA143798, F32 GM096558]
- James S. McDonnell Foundation
- National Brain Tumor Society Defeat GBM initiative
- NATIONAL CANCER INSTITUTE [U54CA143798] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [F32GM096558] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS080944] Funding Source: NIH RePORTER
Ask authors/readers for more resources
The serine-threonine kinase AKT regulates proliferation and survival by phosphorylating a network of protein substrates. Here we describe a kinase-independent function of AKT. In cancer cells harboring gain-of-function alterations in MET, HER2, or Phosphatidyl-Inositol-3-Kinase (PI3-K), catalytically-inactive AKT (K179M) protected from drug-induced cell death in a PH-domain dependent manner. An AKT kinase domain mutant found in human melanoma (G161V) lacked enzymatic activity in-vitro and in AKT1/AKT2 double knockout cells, but promoted growth-factor independent survival of primary human melanocytes. ATP-competitive AKT inhibitors failed to block the kinase-independent function of AKT, a liability that limits their effectiveness compared to allosteric AKT inhibitors. Our results broaden the current view of AKT function and have important implications for the development of AKT inhibitors for cancer.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available