The epidermal growth factor receptor-the prototypic RTK-turns 40

The seminal discovery that the epidermal growth factor receptor (EGFR) possesses intrinsic EGF-stimulated tyrosine kinase activity that serves as a mitogenic signalling mechanism was dependent on two separate lines of research that intersected in the late 1970s and early 1980s, namely studies of retroviral transforming proteins and the identification of growth factor receptor proteins. This historical review outlines the events that ultimately led to the intersection of these two strands of research, resulting from the twin discoveries that many growth factor receptors, including EGFR, are ligand-activated receptor tyrosine kinases (RTKs), and that many retroviral transforming proteins are dysregulated tyrosine kinases that usurp RTK signalling pathways to drive continuous cell proliferation. A French translation of this abstract is available in the supplementary material. This article is part of the discussion meeting issue 'Epidermal growth factor receptor after 40 years'.