Ligand-Induced Transformation by a Noninternalizing Epidermal Growth Factor Receptor
- 23 February 1990
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 247 (4945), 962-964
- https://doi.org/10.1126/science.2305263
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.Keywords
This publication has 26 references indexed in Scilit:
- Anomalous binding of epidermal growth factor to A431 cells is due to the effect of high receptor densities and a saturable endocytic system.The Journal of cell biology, 1988
- The Protein Kinase Family: Conserved Features and Deduced Phylogeny of the Catalytic DomainsScience, 1988
- Ligand-induced endocytosis of the EGF receptor is blocked by mutational inactivation and by microinjection of anti-phosphotyrosine antibodiesCell, 1988
- Overexpression of the human EGF receptor confers an EGF-dependent transformed phenotype to NIH 3T3 cellsCell, 1987
- Requirement for intrinsic protein tyrosine kinase in the immediate and late actions of the EGF receptorNature, 1987
- A tail of two src's: Mutatis mutandisCell, 1987
- Expression in rat fibroblasts of a human transforming growth factor-α cDNA results in transformationCell, 1986
- Different forms of the epidermal growth factor receptor kinase have different autophosphorylation sitesBiochemistry, 1985
- Structure of a Mouse Submaxillary Messenger RNA Encoding Epidermal Growth Factor and Seven Related ProteinsScience, 1983
- Nucleotide sequence of epidermal growth factor cDNA predicts a 128,000-molecular weight protein precursorNature, 1983