A Novel Tyrosine Kinase Expressed in Breast Tumors.
Abstract
The breast tumor kinase Sik (BRK) is distantly related to the Src family of tyrosine kinases and has a similar structure, but it lacks a myristoylation signal. We found that Sik is a nuclear tyrosine kinase that phosphorylates the RNA binding protein Sam68. Sik interacts with Sam68 through both its SH3 and SH2 domains. Transfected Sik and Sam68 colocalize to the nucleoplasm of nontransformed NMuMG mammary epithelial cells, while the human homologue of Sik (BRK) associates with Sam68 and localizes to distinct nuclear structures (SNBs; Sam68 Nuclear Bodies) in the MCF-7 and HT-29 human carcinoma cell lines. The cellular function of Sam68 is not well understood, but its ability to functionally substitute for the HIV-1 Rev protein suggests a role in RNA export and posttranscriptional gene regulation. While Sam68 may be phosphorylated by Srcifamily members during mitosis when the nuclear membrane breaks down, Sik (BRK) is the first identified tyrosine kinase that is capable of phosphorylating Sam68 within the nucleus where it resides during most of the cell cycle. Sam68 is the first identified substrate of the Sik (BRK) kinase. It is possible that Sik (BRK) phosphorylation of Sam68 regulates an aspect of RNA transport and posttranscriptional gene regulation associated with development of breast cancers.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1999
- Accession Number
- ADA378897
Entities
People
- Angela L. Tyner
Organizations
- University of Illinois at Chicago