Brk, a breast tumor-derived non-receptor protein-tyrosine kinase, sensitizes mammary epithelial cells to epidermal growth factor.
brk (breast tumor kinase) shows homology to the src family of non-receptor protein-tyrosine kinases and is expressed in breast carcinomas. In order to investigate the role of brk in breast tumor development, we have examined the growth and transformation properties of human mammary epithelial cells engineered to overexpress Brk. Interestingly, like c-Src, overexpression of Brk leads to sensitization to EGF, and also results in a partially transformed phenotype. Further investigation of the latter activity was attempted by mutational analysis, targeting key residues known to affect tyrosine kinase activity in Src-like kinases. Mutation of amino acid residue Lys-219 to Met, by analogy to Src, abolished both kinase activity and transformation capacity. Mutation of amino acid residue Tyr-447 to Phe, however, resulted in a decrease in transforming potential without affecting kinase activity. These results suggest that while Src and Brk share some functional properties, they act differently during transformation. These differences are discussed in the context of the mechanisms underlying breast cancer development.
Kamalati
T
T
Section of Cell Biology and Experimental Pathology, Institute of Cancer Research, Sutton, Surrey, United Kingdom.
Jolin
H E
HE
Mitchell
P J
PJ
Barker
K T
KT
Jackson
L E
LE
Dean
C J
CJ
Page
M J
MJ
Gusterson
B A
BA
Crompton
M R
MR
D016475:3T3 Cells; D000818:Animals; D001940:Breast / Q000201:enzymology; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000008:administration & dosage*; D004848:Epithelium / Q000201:enzymology; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D051379:Mice; D009363:Neoplasm Proteins; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*
D009363:Neoplasm Proteins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; C088375:PTK6 protein, human