A Novel Tyrosine Kinase Expressed in Breast Tumors
Abstract
Efforts to identify genes that regulate intestinal epithelial cell differentiation led to the isolation of a novel epithelial-specific tyrosine kinase named Sik, for Src-related intestinal kinase. We identified the human homologue of Sik and determined that it is the breast tumor kinase BRK, which had been isolated from a metastatic breast tumor. Sik/BRK is expressed in differentiating epithelial cells of the skin and gastrointestinal tract. While BRK is induced in a high percentage of breast tumors examined, we could not detect Sik/BRK expression at any stage of normal mammary gland development. In breast cancer cell lines, BRK is in novel nuclear structures called Sam68/SLM nuclear bodies (SNBs), where it associates with the RNA-binding protein Sam68. Phosphorylation of Sam68 by Sik/BRK inhibits Sam68 RNA-binding and the ability of Sam68 to act as an HIV1 Rev cellular homologue in nuclear RNA export. Sam68 has been shown to play a positive role in promoting mitosis, and is a member of a growing family of RNA-binding proteins called STAR (Signal Transducers and Activators of RNA). Sik/BRK may regulate gene expression associated with breast cancer development by modifying the activities of the Sam68 and related STAR proteins.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2000
- Accession Number
- ADA390033
Entities
People
- Angela L. Tyner
Organizations
- University of Illinois at Chicago