A Novel Tyrosine Kinase Expressed in Breast Tumors
Final rept. 19 Aug 1996-19 Aug 2000
ILLINOIS UNIV AT CHICAGO
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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. SikBRK 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 SikBRK expression at any stage of normal mammary gland development. In breast cancer cell lines, BRK is in novel nuclear structures called Sam68SLM nuclear bodies SNBs, where it associates with the RNA-binding protein Sam68. Phosphorylation of Sam68 by SikBRK 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. SikBRK may regulate gene expression associated with breast cancer development by modifying the activities of the Sam68 and related STAR proteins.
- Anatomy and Physiology
- Medicine and Medical Research