-transparent.png){kind=logo}
We have identified a new tyrosine kinase from human breast cancer cells called Rak (a Russian word for cancer) that shares 51% identity with c-Src. Sequencing of the full-length complementary DNA revealed that Rak is a tyrosine kinase with a molecular weight of 54,000 that contains SH2 and SH3 domains, as well as tyrosine residues analogous to the autophosphorylation and regulatory tyrosines of the Src family. Biochemical and site-directed mutagenesis analyses revealed that a carboxy-terminal peptide of p54rak was phosphorylated by a cytoplasmic tyrosine kinase (CSK) and that, as in the Src family, it is the COOH-terminal tyrosine that is phosphorylated by CSK. However, there were some properties of Rak that are distinct from Src-like kinases: (a) expression of Rak was predominantly in epithelial-derived cell lines and tissues, especially normal liver and kidney, and cell lines of breast and colon origin; (b) Rak does not harbor the NH2-terminal glycine essential for myristylation and membrane localization; and (c) Rak possesses a putative bipartite nuclear localization signal in the SH2 domain, and subcellular fractionation studies revealed that p54rak resides predominantly in the nucleus. In addition, p54rak was overexpressed in subsets of primary human epithelial tumors, suggesting that p54rak may have a role in human cancer. Thus, Rak is a novel epithelial-associated nuclear tyrosine kinase that may represent a unique subfamily of the Src-related kinases.
W G Cance, and
R J Craven, and
M Bergman, and
L Xu, and
K Alitalo, and
E T Liu
August 2009,
Cell cycle (Georgetown, Tex.),
W G Cance, and
R J Craven, and
M Bergman, and
L Xu, and
K Alitalo, and
E T Liu
January 2002,
Bioconjugate chemistry,
W G Cance, and
R J Craven, and
M Bergman, and
L Xu, and
K Alitalo, and
E T Liu
December 1992,
Biochemical and biophysical research communications,
W G Cance, and
R J Craven, and
M Bergman, and
L Xu, and
K Alitalo, and
E T Liu
January 1995,
Oncogene,
W G Cance, and
R J Craven, and
M Bergman, and
L Xu, and
K Alitalo, and
E T Liu
August 2004,
The Biochemical journal,
W G Cance, and
R J Craven, and
M Bergman, and
L Xu, and
K Alitalo, and
E T Liu
June 1987,
Molecular and cellular biology,
W G Cance, and
R J Craven, and
M Bergman, and
L Xu, and
K Alitalo, and
E T Liu
October 1993,
Oncogene,
W G Cance, and
R J Craven, and
M Bergman, and
L Xu, and
K Alitalo, and
E T Liu
December 1990,
Oncogene,
W G Cance, and
R J Craven, and
M Bergman, and
L Xu, and
K Alitalo, and
E T Liu
September 1994,
Seikagaku. The Journal of Japanese Biochemical Society,
W G Cance, and
R J Craven, and
M Bergman, and
L Xu, and
K Alitalo, and
E T Liu
July 2002,
Molecular and cellular biology,
