Ligand-Induced Transformation by a Noninternalizing Epidermal Growth Factor Receptor

• DOI: 10.1126/science.2305263
• Publication Date: 2006-10-05T22:10:14Z
• Authors: Alan Wells; John B. Welsh; Cheri S. Lazar; H. Steven Wiley; Gordon N. Gill; Michael G. Rosenfeld
• Keywords: Internalization; Cell surface receptor

Identification of a mutant epidermal growth factor (EGF) receptor that does not undergo downregulation has provided genetic probe to investigate the role internalization in ligand-induced mitogenesis. Contact-inhibited cells expressing this internalization-defective exhibited normal mitogenic response at significantly lower ligand concentrations than did wild-type receptors. A transformed phenotype and anchorage-independent were observed failed elicit these responses These findings imply activation protein tyrosine kinase activity cell membrane is sufficient for growth-enhancing effects EGF. Thus, can serve as an attenuation mechanism, without which transformation ensues.