FGFR3 and SH2-B Interactions in Breast Cancer

Eric Rogers

Appointment Period: 2005-2006 / Grant Year: [21]

My research focused on studying the function of a altered version of FGFR3 present in breast cancer. Previously, the expression of this unusual splice variant of FGFR3 was detected in breast cancer tissues and breast cancer cell lines, but not in normal breast tissues. Mutations in the receptor tyrosine kinase FGFR3 have been associated with various cancers. Normally, FGFR3 is localized on the cell surface in order to bind to extracellular ligands, however, in both breast cancer tissues and cell lines this unusual FGFR3 variant was reportly mislocalized to the nucleus. To verify this we examined the subcellular localization of the FGFR3 variant by expressing constructs in mouse fibroblasts. Using immunohistochemistry, we observed that the FGFR3 variant is localized in a symmetric perinuclear ring. The meaning of this localization is currently unknown. Concurrently, we examined the previously described physical interaction between FGFR3 and the signaling adaptor protein SH2-B in greater molecular detail. We co-expressed various constructs of FGFR3 and SH2-B in human embryonic cells and performed co-immunoprecipitation experiments to assay their physical interactions.

PUBLICATIONS (resulting from this training)

Meyer, A. N., E. Rogers, E. Katbab, D. J. Donoghue. 2006. The adapter protein SH2-B stimulates increased tyrosine phospohorylation of FGFR3. In preparation.