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The QBI Online Seminar Series is presenting Jennifer Kavran, an assistant professor of Biochemistry and Molecular Biology at the Bloomberg School of Public Health at Johns Hopkins University. Dr. Kavran's lab is focused on understanding the regulation of the Hippo core kinase cassette using a multiprong approach including cell biology, enzymology, biophysics, and structural biology. Her long-term goal is to understand the molecular mechanisms that regulate signal transduction pathways. Dr. Kavran's interest in structure-function began as graduate student at Yale in the laboratory of Tom Steitz where she determined the structure of pyrrolysyl-tRNA synthetase. For her post-doc, she shifted her focus to signaling pathways. In the laboratory of Dan Leahy at Johns Hopkins, she uncovered how ligand binding activates the receptor tyrosine kinase IGF1R.
Hippo signal transduction relies on the activity of a core kinase cassette that can be activated by multiple upstream signals. Dr. Kavran's lab wanted to rationalize how multiple signals could each promote activation of the same kinase, MST2. They performed a biophysical analysis of the entire complement of SARAH domains to determine how these interactions could influence MST2 homodimerization. They investigated the biochemical nature of MST2 activation and demonstrated increasing proximity of MST2 kinase domains is sufficient to trigger autophosphorylation. They showed in cells that events known to stimulate signal transduction also increase both MST2 proximity and autophosphorylation. Together, Dr. Kavran's lab's work reveals that a single molecular mechanism controls MST2 activation.
Talk title: A universal mechanism for activation of MST2 during Hippo signal transduction
Hosted by: Natalia Jura
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