BBB seminar: Bruce J. Mayer - NB! Postponed
Using phosphotyrosine binding domains to interrogate the state of cell signaling
Bruce J. Mayer
Department of Genetics and Genome Sciences, University of Connecticut School of Medicine, Farmington, CT, USA
In multicellular organisms, tyrosine phosphorylation controls many important cellular behaviors such as proliferation, differentiation, adhesion, and motility. Downstream signaling depends on the combined activities of tyrosine kinases, tyrosine phosphatases, and modular phosphotyrosine binding domains such as SH2 domains. The complement of ~120 SH2 domains represents the molecular apparatus used by human cells to interpret changes in tyrosine phosphorylation. We have developed a molecular approach, termed SH2 profiling, that uses SH2 domains to interrogate the state of phosphotyrosine signaling in the cell. We have used SH2 profiling to investigate the dynamics of the response to activation of receptor tyrosine kinases. We have also used super-resolution imaging to visualize SH2 binding in living cells, providing insight into the dynamics and spatial organization of phosphotyrosine signaling complexes. Finally, SH2 profiling can be used to classify tumor cells and predict clinical outcomes, such as risk of progression or response to therapy. Currently, we are combining SH2 profiling with computational modeling and biochemical approaches to gain mechanistic insight into specific phosphotyrosine-mediated interactions that can lead to differences in downstream signaling and in outcomes for cancer patients.
Chairperson: James Lorens, Department of Biomedicine