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Receptor tyrosine kinase is a membrane protein that regulates cell growth and differentiation. Ligand binding to the extracellular region triggers its function as a kinase in the intracellular region. Yet, it is still not known how the “signal” encoded by ligand binding to the receptor is transmitted across the membrane. Answering this fundamental question requires analysis in detail on the transmembrane and the juxtamembrane regions of the receptor. This review focuses on recent progress in structural work for these regions to understand the activation mechanism of EGFR, arguably one of the most intensively studied membrane receptors. [ABSTRACT FROM AUTHOR]