Control of Hydrophobic Helix Topography in Membranes by Lipid Composition

Abstract

Receptor Tyrosine Kinases (RTKs) play key roles in cell growth, differentiation, metabolism, and migration. These single-pass receptors conduct biochemical signals by dimerizing in the plasma membrane. The process of lateral dimerization, which controls the distribution between inactive monomers and active dimers, serves as a key regulator of the biochemical processes that determine cell fate. Enhanced dimerization leads to persistent autocrine activation and tumorigenesis, or impaired growth. An understanding of the dimerization process as a function of interaction energies, protein concentration and ligand concentration, is lacking. Our laboratory is developing methodologies that yield quantitative information about RTK dimerization and activation in cellular membranes. These methods will enable biomedical researchers to study the quantitative aspects of signal transduction in the context of the biological membrane.