Work Links to Discovery Made at Rockefeller 86 Years Ago
The three-dimensional picture of a cancer-causing protein illuminates how a mutated gene transforms cells into cancer, report scientists from the Howard Hughes Medical Institute at The Rockefeller University in the Feb. 13 Nature. The determination of this structure clarifies earlier models that sought to explain how the gene, called src, works and offers new information for designing drug therapies to fight cancers.
"These findings help to explain how tinkering with just one protein produces changes in cell behavior," said senior author John Kuriyan, Ph.D., Rockefeller professor and HHMI investigator. "This gives us a better understanding of the breakdown of controls that lead to cancer." Kuriyan heads one of the university's laboratories of Molecular Biophysics.
Cells rely on proteins to regulate their differentiation and growth. Mutations that alter the normal function of control proteins result in unchecked growth and differentiation--cancer. In a process called phosphorylation--often the first step of signal transmission inside a cell--an enzyme called a kinase attaches a highly charged phosphate group to a tyrosine, one of the 20 amino acids that make proteins, acting as a molecular switch that turns proteins off and on.
In this study, Kuriyan and co-workers Frank Sicheri, Ph.D., and Ismail
Moarefi, Ph.D., determined the three-dimensional structure of Hck, one member
of the Src family of very closely related tyrosine kinases, named for
src, the first oncogene that was found to be the mutated form of a
cellular protein. The Src family plays an important role in regulating the
body's immune system and other cellular behavior. Src is found in nearly all
cells of the body, but Hck primarily arises in cells related to the immune
system, such as macrophages and B cells. In a related paper
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