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

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1172-1180
Number of pages9
JournalJournal of Virology
Volume69
Issue number2
Publication statusPublished - Jan 1 1995
Externally publishedYes

Fingerprint

protein phosphorylation
fibroblasts
Tyrosine
tyrosine
phosphorylation
phosphotransferases (kinases)
Phosphotransferases
Fibroblasts
Oncogene Proteins
Phosphorylation
point mutation
Point Mutation
Epidermal Growth Factor Receptor
Avian erythroblastosis virus
Alpharetrovirus
mutation
Calcium-Sensing Receptors
Leukemia, Erythroblastic, Acute
Mutation
receptors

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

A minor tyrosine phosphorylation site located within the CAIN domain plays a critical role in regulating tissue-specific transformation by erbB kinase. / Chan, C. M.; Shu, H. K.G.; Ravi, L.; Pelley, R. J.; Shu, H.; Kung, H. J.

In: Journal of Virology, Vol. 69, No. 2, 01.01.1995, p. 1172-1180.

Research output: Contribution to journalArticle

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