Small Scale Proteomics Approach for Identifying Proteins Regulated by the Breast Tumor Kinase BRK Signal Transduction Pathway.

摘要

The breast tumor kinase BRK is not expressed in normal breast tissue, but is expressed in a high proportion of breast tumors and breast tumor cell lines. Because of its high expression in breast tumor cells, we propose that BRK regulates signaling that leads to protein expression that contributes to breast cancer development. We are currently examining changes in protein expression due to ectopic expression of BRK in the normal murine mammary gland cell line NMuMG. Availability of the human genome sequence has led to our discovery of tight linkage of the Srm tyrosine kinase gene to the BRK gene on human chromosome 2Oq13.3. Because of the tight linkage of these two genes, it is possible that they are coregulated in breast cancer cells. Expression of Srm in normal breast tissue and breast tumor cells is currently under investigation. While BRK has a low degree of homology to other intracellular tyrosine kinases including Srm, Frk/Rak, and Src42A/Dsrc4l, the exon structures of these kinases is highly conserved, and distinct from other families of intracellular kinases including c-Src. Frk/Rak, is also expressed in breast cancers, suggesting a general role for the BRK family of kinases this disease.