The Role of the Novel Nuclear Tyrosine Kinase, RAK, in Breast Cancer Biology
Abstract
The Rak tyrosine kinase is a 54 kDa protein with SH2 and SH3 domains at its amino terminus. Although Rak resembles the Src-related kinases structurally, Rak differs in that it is expressed primarily in epithelial cells and localizes to the nucleus. We have found that Rak inhibits the growth of NIH 3T3 cells as determined by a colony formation assay. Furthermore, induction of Rak expression from a dexamethasone-inducible promoter leads to enlarged, flattened cells. There are two potential effectors of Rak's growth inhibitory activity, Rak binds to the retinoblastoma tumor suppressor protein pRb and the cell cycle regulatory kinase CDC2. However, we have found that Rak inhibited growth equally in the Rb+ osteosarcoma cell line U2- Os and the Rb-minus osteosarcoma cell line Saos-2, suggesting that binding to Rb is not required for Rak's biological activity. The parallel experiment for CDC2 was not possible because CDC2 is an essential gene. Finally, we have found that Rak localizes to chromosome 6q21. This site is frequently altered in a variety of human tumors, including breast tumors. Thus, Rak is a kinase with growth inhibitory activity that localizes to a putative tumor suppressor locus.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1997
- Accession Number
- ADA328990
Entities
People
- Edison Liu
- Rolf Craven
Organizations
- University of North Carolina at Chapel Hill