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

Hui Kuo G Shu, Robert J. Pelley, Hsing-Jien Kung

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)9103-9107
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume87
Issue number23
StatePublished - 1990
Externally publishedYes

Keywords

  • Cellular transformation
  • Erythroblastosis
  • Retrovirus
  • Sarcoma
  • Tyrosine kinase

ASJC Scopus subject areas

  • Genetics
  • General

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