Receptor Tyrosine Kinases: Dimerization, Structure, and Function
Prof Hristova has an interest in the structure, assembly, and function of biological membranes. She uses novel biophysical and imaging techniques to study the the energetics of biomolecular interactions of several different RTKs within mammalian biological membranes to reveal novel insights into receptor dimerization.
Receptor Tyrosine Kinases (RTKs) are membrane receptors that regulate growth, differentiation, and tissue development. Dysregulation of RTK signaling can lead to disease, including a variety of cancers and growth disorders. RTK-specific therapies are being sought, but current treatments have not produced the anticipated positive results. The lack of basic knowledge about RTK activation is one bottleneck in the development in efficient therapies. Indeed, recent studied in the field have suggested that the canonical model of ligand-induced dimerization and activation, which has shaped the field since the discovery of RTKs, is likely incomplete.
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Speaker: Prof Kalina Hristova Department of Materials Science and Engineering and Institute for NanoBioTechnology Johns Hopkins University |
The work in our lab has suggests that all RTKs follow a more complex model of activation, characterized by the (i) existence of RTK unliganded dimer, (ii) varying levels of unliganded dimer stabilities (and thus dimer abundance at physiological concentrations) and (iii) ligand-induced dimer structural changes that propagates to the intracellular domains. I will present data that demonstrate that the ligand controls the structure of the TM domain by triggering a switch to a specific configuration, and the resulting structure of the TM dimer controls the activity of the receptor.
No RSVP required.
