BRK, Active

BRK is another member of the non-receptor tyrosine kinases (PTKs) that contains an amino terminal SH3 and SH2 domains as well as the catalytic domain (1). Although BRK shows strongest sequence similarity to members of the Src family, there are several key structural and regulatory differences that place it on its own amongst non-receptor PTKs. The genomic structure of BRK consists of 8 exons, whose boundaries are distinct from other non-receptor PTK family members (2). Alternate splicing of the primary BRK transcript generates a distinct mRNA which encodes a truncated protein consisting of an SH3 domain and a novel C-terminal proline rich sequence. Brk transcript is expressed in the human breast tumor cell line and expression of a tumor derived Brk cDNA in mouse embryonic fibroblasts and human mammary epithelial cells supports anchorage independent growth, and in the latter potentiates the mitogenic response to epidermal growth factor. Brk expression is low or undetectable in normal mammary tissue and benign lesions. However, approximately two-thirds of breast tumors express appreciable levels and 27% of tumors over express BRK by fivefold or more (up to 43x). This expression pattern is mirrored in comparison of cell lines derived either from normal mammary epithelial cells or from carcinomas (3).