Control of Akt Activity in Prostate Cancer
Abstract
Akt is an important kinase in prostate cancer, being activated downstream of growth factor receptors and downstream of PTEN mutations. Akt activity is controlled through two mechanisms, phosphorylation by Pdk1 and by Pdk2. Pdk2 is the mTORC2 complex, which controls phosphorylation of Akt at Ser473. We have recently shown that IKK alpha, a component of the IKK complex which controls NF-kappaB activation, regulates mTORC1 downstream of Akt activation. Here we explore a role for IKK alpha in controlling mTORC2 activity. Our data indicate that IKK alpha associates with mTORC2 in prostate cancer cells and regulates its activity towards Akt at Ser473. Knockdown of IKK alpha blocks Akt activity in prostate cancer cells. We propose to determine the mechanisms whereby IKK alpha controls mTORC2 activity and to determine if loss of IKK alpha in a animal model for prostate cancer will block progression of the disease. We will test an IKK alpha inhibitor as a potential therapeutic for prostate cancer in this model.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2009
- Accession Number
- ADA512632
Entities
People
- Albert S Baldwin
Organizations
- University of North Carolina at Chapel Hill