A minor tyrosine phosphorylation site located within the CAIN domain plays a critical role in regulating tissue-specific transformation by erbB kinase

C. M. Chan, H. K.G. Shu, L. Ravi, R. J. Pelley, H. Shu, H. J. Kung

研究成果: 雜誌貢獻文章同行評審

11 引文 斯高帕斯(Scopus)

摘要

Avian c-erbB encodes a protein that is homologous to the human epidermal growth factor receptor. Truncation of the amino-terminal, ligand-binding domain of this receptor results in an oncogene product which is a potent inducing agent for erythroleukemias but not fibrosarcomas in chickens. Here we show that mutation of a single tyrosine residue, p5, in the carboxyl terminus of the erbB oncogene product allows it to become sarcomagenic in vivo and to transform fibroblasts in vitro. Mutations of other autophosphorylation sites do not generate comparable effects. The increased transforming activity of the p5 mutant is accompanied by an elevated level of mitogen-activated protein kinase phosphorylation. By analogy to the human epidermal growth factor receptor, p5 is a minor autophosphorylation site and is located in a domain known to be involved in regulating calcium influx and receptor internalization (CAIN domain). This area of the erbB product has been found to be repeatedly deleted in various sarcomagenic avian erythroblastosis virus isolates. We precisely deleted the CAIN domain and also made point mutations of the acidic residues within the CAIN domain. In both cases, fibroblast-transforming potential is activated. We interpret these data to mean that p5 and its surrounding region negatively regulate fibroblast-transforming and sarcomagenic potential. To our knowledge, this represents the first point mutation of an autophosphorylation site that activates erbB oncogenicity.
原文英語
頁(從 - 到)1172-1180
頁數9
期刊Journal of Virology
69
發行號2
DOIs
出版狀態已發佈 - 一月 1 1995
對外發佈

ASJC Scopus subject areas

  • 微生物學
  • 免疫學
  • 昆蟲科學
  • 病毒學

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