Breast Tumor Kinase (BRK) Signaling in Breast Cancer
Abstract
The breast tumor kinase BRK is expressed in a high percentage of human breast tumors and breast tumor cell lines. We found that BRK is a nuclear tyrosine kinase that phosphorylates the RNA binding protein Sam68 (Src associated during mitosis, 68 kDa). BRK and Sam68 colocalize in Sam68/SLM nuclear bodies (SNBs) in human breast tumor cell lines. In functional studies, expression of BRK abolished the ability of Sam68 to bind RNA and act as a cellular Rev homologue. In addition to Sam68, we found that BRK also phosphorylates the Sam68-like mammalian proteins SLM-1 and SLM-2. We examined expression of Sam68, SLM-1, and SLM-2 in the mouse mammary gland using RNase protection assays. In the normal mouse mammary gland only expression of Sam68 was detected. We are currently examining expression of SLM-I and SLM-2 in human breast tumor cell lines. While Sam68 is a substrate for Src family kinases during mitosis, BRK is the first identified tyrosine kinase that can phosphorylate Sam68 and regulate its activity within the nucleus, where it resides during most of the cell cycle. Since Sam68 has been implicated in cell cycle regulation, increased expression of BRK may alter the ability of Sam68 to regulate cell growth.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2002
- Accession Number
- ADA407665
Entities
People
- Angela L. Tyner
Organizations
- University of Illinois at Chicago