Avian c-erbB is activated to a leukemia oncogene following truncation of its amino-terminal, ligand-binding domain by retroviral insertion. The insertionally activated transcripts encode protein products that have constitutive tyrosine kinase activity and that can induce erythroleukemia but not sarcomas. We have found that a single point mutation within the ATP-binding pocket of the tyrosine kinase domain in this truncated molecule can increase the ability of this oncogene to induce anchorage-independent growth of fibroblasts in vitro and fibrosarcoma formation in vivo. Associated with this increased transforming potential is a corresponding increase in the kinase activity of the mutant erbB protein product. The mutation, which converts a valine to isoleucine at position 157 of the insertionally activated c-erbB product, is at a residue that is highly conserved within the protein kinase family. To our knowledge, this is the first demonstration of a point mutation in the ATP-binding pocket that activates a tyrosine kinase.
|頁（從 - 到）||9103-9107|
|期刊||Proceedings of the National Academy of Sciences of the United States of America|
|出版狀態||已發佈 - 十二月 1 1990|
ASJC Scopus subject areas
Shu, H. K. G., Pelley, R. J., & Kung, H. J. (1990). Tissue-specific transformation by epidermal growth factor receptor: A single point mutation within the ATP-binding pocket of the erbB product increases its intrinsic kinase activity and activates its sarcomagenic potential. Proceedings of the National Academy of Sciences of the United States of America, 87(23), 9103-9107. https://doi.org/10.1073/pnas.87.23.9103