Our laboratory is currently focusing on the elucidation of the mechanism by which tyrosine kinases mediate signals to the cytoskeleton during mouse development as well as in cancer using gene targeting technology and mouse genetics. We are also investigating the connection between tyrosine kinases and human malignancies at the interface of the cytoskeleton. Like other abnormal genes that are linked to cancer, the oncogene v-src has multiple effects on mammalian cells, including, most dramatically, the induction of cellular transformation, which is believed to correspond to the change of normal cells to cancer.
Most cancer cells have elevated levels of tyrosine kinase activity.
Therefore, the v-Src protein lacks this regulatory mechanism and is always active. Another class of PTKs, Csk and Ctk, phosphorylate in vitro the regulatory tyrosine conserved within the Src family. By phosphorylation at the key tyrosine residue, these PTKs regulate cellular Src, which otherwise is potentially oncogenic. Further analysis of cells isolated from mutant embryos suggested that the phenotype of csk homozygous mutants may result from rearrangement of the cytoskeleton. Interestingly, one of the cytoskeletal proteins hyperphosphorylated in csk mutant cells is also known to be amplified in a population of breast cancers with poor prognosis.