Single Molecule Imaging of Human Epidermal Growth Factor Receptors

摘要: Biophysical Society Meeting 2014.The human epidermal growth factor receptor (HER/ErbB) family of tyrosine kinases encompasses transmembrane signaling proteins important for cellular growth, differentiation, and survival. The four members this (EGFR, HER2, HER4 the HER3 pseudokinase receptor) are able to bind numerous different ligands, leading their homo hetero-oligomerization subsequent activation. This combinatorial potential gives rise a diverse output, which is strongly affected by misregulation any one receptor. For example, mutations in EGFR HER2 overexpression primary mechanisms driving lung breast cancer, respectively. Under these conditions, heterodimerization receptors with confers resistance tumors treated HER2-targeted therapeutics. molecular basis heterodimeric interactions regulation factors remains poorly understood. HER heterodimers have never been observed directly, existence remain inferred from analysis downstream signaling. To understand scope specificity between its active homologs, we seek directly investigate underlying activation using high resolution fluorescence microscopy. We quantify extent response ligand binding both live cell single molecule tracking stochastic optical reconstruction microscopy (STORM). These techniques allow us probe timescales as function binding, dependence on density at membrane surface, heterodimer formation. work aims contribute fundamental understanding mechanism help advance development new therapeutics targeting aberrant cross-talk among disease.