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

H. K.G. Shu, R. J. Pelley, H. J. Kung

研究成果: 雜誌貢獻文章

39 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
頁(從 - 到)9103-9107
頁數5
期刊Proceedings of the National Academy of Sciences of the United States of America
87
發行號23
DOIs
出版狀態已發佈 - 十二月 1 1990
對外發佈Yes

ASJC Scopus subject areas

  • General

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