Cell and Molecular Biology
Lck; Leukemia; CTV-1; Cancer Biology
Leukemia is a type of cancer that develops in blood-forming tissues of the immune system. These tissues can include the bone marrow or sites within the lymphatic system such as the lymph nodes. Leukemia progresses from a mutational event within a white blood cell. Often this mutation alters the cell’s normal life cycle, resulting in uninhibited cell division and growth. With this uncontrolled cell proliferation, mutated white blood cells accumulate and begin interfering with the functioning of healthy cells.
Scientists are unsure of the exact mechanisms required for leukemia development. However, recently scientists identified four characteristic mutations in the protein tyrosine kinase, Lck, found specifically in the CTV-1 leukemia cell line. Lck is suspected to play an important regulatory role in immune system cell growth. In this honors project, I introduced these mutations into the Lck gene and produced the wildtype and the mutant enzymes. By comparing the mutated enzyme’s activity to the wild-type enzyme’s activity, we can potentially better understand how a mutation in Lck could stimulate cell proliferation.
One of the mutations is an insertion mutation located in the linker region of the Lck’s structure. It is a potentially interesting alteration that could result in the enzyme’s constitutive activation. This inability for the enzyme to be turned off not only demonstrates how mutated Lck could be contributing to cancer progression but also reveals valuable knowledge about the functional importance of the linker region in Lck.