The Role of AKT2 in Human Breast Cancer
Abstract
Frequent alterations of AKT2 oncogene have been frequently detected in human malignancies, including breast carcinoma (1, 2). To better understand the role of AKT2 in breast carcinogenesis, we have isolated a novel protein, APBP, that binds to and is phosphorylated by AKT2. Recent studies showed that p2l-activated kinase-1 (PAK1) is activated by AKT2 and that the activated PAK1 induces BAD phosphorylation at Ser112 and Ser136. However, the mechanism by which AKT2 activates PAK1 is unknown. We have recently demonstrated that APBP mediates AKT2 activation of PAK1 by directly binding to PAK1. We have mapped the binding site between APBP and PAK1, i.e., the first and third SH3 domains of APBP interact with a proline-rich region of PAK1. Furthermore, we have shown that APBP protects cells from apoptosis induced by DNA damage and expression of proapoptotic protein Bad. In addition, we have demonstrated that AKT2 is activated by cellular stress and TNFalpha in human epithelial cells. The activated AKT2 inhibits both LINK and p38 stress kinase activation and protects cells from UV, Heat shock and TNFalpha-induced apoptosis. We have also demonstrated that AKT2-inhibited JNK1 activation is mediated by AKT2-induced NF kappa B.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2002
- Accession Number
- ADA407211
Entities
People
- Jin Q. Cheng
- Zeng Q. Yuan
Organizations
- University of South Florida