@article {Wells962, author = {Wells, A and Welsh, JB and Lazar, CS and Wiley, HS and Gill, GN and Rosenfeld, MG}, title = {Ligand-induced transformation by a noninternalizing epidermal growth factor receptor}, volume = {247}, number = {4945}, pages = {962--964}, year = {1990}, doi = {10.1126/science.2305263}, publisher = {American Association for the Advancement of Science}, abstract = {Identification of a mutant epidermal growth factor (EGF) receptor that does not undergo downregulation has provided a genetic probe to investigate the role of internalization in ligand-induced mitogenesis. Contact-inhibited cells expressing this internalization-defective receptor exhibited a normal mitogenic response at significantly lower ligand concentrations than did cells expressing wild-type receptors. A transformed phenotype and anchorage-independent growth were observed at ligand concentrations that failed to elicit these responses in cells expressing wild-type receptors. These findings imply that activation of the protein tyrosine kinase activity at the cell membrane is sufficient for the growth-enhancing effects of EGF. Thus, downregulation can serve as an attenuation mechanism, without which transformation ensues.}, issn = {0036-8075}, URL = {https://science.sciencemag.org/content/247/4945/962}, eprint = {https://science.sciencemag.org/content/247/4945/962.full.pdf}, journal = {Science} }