Tyrosine kinase activity may be necessary but is not sufficient for c-erbB1-mediated tissue-specific tumorigenicity

Denise C. Connolly, Sonja L. Toutenhoofd, Nita Jane Maihle

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Expression of mutant avian c-erbB1 genes results in tissue-specific transformation in chickens. Site-directed mutagenesis was used to generate kinase-defective mutants of several tissue-specific v-erbB transforming mutants by replacement of the ATP-binding lysine residue in the kinase domain with an arginine residue. These kinase-defective v-erbB mutants were analyzed for their in vitro and in vivo transforming potentials. Specifically, kinase-defective mutants of erythroleukemogenic, hemangioma-inducing, and sarcomagenic v-erbB genes were assessed for their oncogenic potential. In vitro transformation potential was assessed by soft-agar colony formation in primary cultures of chick embryo fibroblasts (CEF). In vivo transformation potential was determined by infection of 1-day-old line 0 chicks with concentrated recombinant retrovirus and then monitoring of birds for tumor formation. These transformation assays demonstrate that kinase activity is absolutely essential for transformation by tissue-specific transforming mutants of the avian c-erbB1 gene. Since all of the tissue-specific v-erbB mutants characterized to date exhibit tyrosine kinase activity in vitro but do not transform all tissues in which they are expressed, we conclude that v-erbB-associated tyrosine kinase activity may be necessary but is not sufficient to induce tumor formation.

Original languageEnglish (US)
Pages (from-to)6804-6810
Number of pages7
JournalJournal of Virology
Volume68
Issue number10
StatePublished - Oct 1 1994
Externally publishedYes

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Protein-Tyrosine Kinases
tyrosine
phosphotransferases (kinases)
erbB-1 Genes
Phosphotransferases
mutants
Retroviridae
chicks
Chick Embryo
Hemangioma
Site-Directed Mutagenesis
hemangioma
Lysine
Agar
Birds
Arginine
neoplasms
Chickens
genes
Neoplasms

ASJC Scopus subject areas

  • Immunology

Cite this

Tyrosine kinase activity may be necessary but is not sufficient for c-erbB1-mediated tissue-specific tumorigenicity. / Connolly, Denise C.; Toutenhoofd, Sonja L.; Maihle, Nita Jane.

In: Journal of Virology, Vol. 68, No. 10, 01.10.1994, p. 6804-6810.

Research output: Contribution to journalArticle

Connolly, Denise C. ; Toutenhoofd, Sonja L. ; Maihle, Nita Jane. / Tyrosine kinase activity may be necessary but is not sufficient for c-erbB1-mediated tissue-specific tumorigenicity. In: Journal of Virology. 1994 ; Vol. 68, No. 10. pp. 6804-6810.
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