Tamoxifen Dependent Interaction Between the Estrogen Receptor and a Novel P21 Activated Kinase
Abstract
The estrogen receptor a (Er-alpha) plays an important role in breast cancer and a large fraction of Er-alpha positive breast cancers respond to tamoxifen. We cloned a novel p21 activated kinase (PAK), termed PAK6, which binds to the androgen receptor (AR) and selectively to the tamoxifen liganded Era. PAKs are a family of serine/threonine kinases that bind to and are regulated by the Rho family small (p21) GTPases, Cdc42 and Rac. PAKS are involved in translating extracellular signals into cellular responses. Although PAK6 binds to Cdc42, it lacks the Cdc42 regulated autoinhibitory domain founding other PAKs and can instead be activated by steroid receptor binding. Binding is mediated by at least two sites on PAK6, one at the N-terminus and another toward the middle of the protein. PAK6 inhibits Er-alpha and AR transcriptional activity. PAK6 is highly expressed in brain and testes, is also expressed in mammary epithelium and prostate, and its expression in breast cancer cell lines has been confirmed by a polyclonal antibody. Further studies of PAK6 protein expression in breast cancer are in progress, and breast cancer cell lines expression wildtype and mutant PAK6 have been generated to assess functions in breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2003
- Accession Number
- ADA424652
Entities
People
- Steven P Balk
Organizations
- Beth Israel Deaconess Medical Center