Disease tropism of c-erbB

Effects of carboxyl-terminal tyrosine and internal mutations on tissue-specific transformation

R. J. Pelley, Nita Jane Maihle, C. Boerkoel, H. K. Shu, T. H. Carter, C. Moscovici, H. J. Kung

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Avian leukosis virus induces erythroleukemia in chickens by proviral insertional mutation of the proto-oncogene c-erbB. The product of the insertionally activated c-erbB locus lacks the extracellular ligand-binding domain and is strictly leukemogenic. It has previously been demonstrated that the disease spectrum associated with aberrant c-erbB expression can be expanded by structural perturbation of the cytoplasmic domain of this protein. In this report, we use mutagenesis and retroviral vectors to identify specific mutations in the carboxyl-terminal domain of the insertionally activated c-erbB product that are sufficient to activate the sarcomagenic potential of this protein. Interestingly, a point mutation in the kinase domain appears to be sufficient for sarcomagenic activation. However, removal of the terminal tyrosine residue of the c-erbB product, implicated in modulating kinase activity, does not lead to a fully transforming phenotype. These studies suggest that there are multiple ways to activate the fibroblast-transforming potential of the insertionally activated c-erbB product. The conformation of this protein may play a more significant role in oncogenic activation than the phosphorylation status of the putative carboxyl-terminal autophosphorylation site.

Original languageEnglish (US)
Pages (from-to)7164-7168
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume86
Issue number18
DOIs
StatePublished - Jan 1 1989

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Tropism
Tyrosine
Phosphotransferases
Avian Leukosis Virus
Leukemia, Erythroblastic, Acute
Protein Conformation
Mutation
Proto-Oncogenes
Point Mutation
Mutagenesis
Chickens
Fibroblasts
Phosphorylation
Ligands
Phenotype
Proteins
Protein Domains

ASJC Scopus subject areas

  • General

Cite this

Disease tropism of c-erbB : Effects of carboxyl-terminal tyrosine and internal mutations on tissue-specific transformation. / Pelley, R. J.; Maihle, Nita Jane; Boerkoel, C.; Shu, H. K.; Carter, T. H.; Moscovici, C.; Kung, H. J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 86, No. 18, 01.01.1989, p. 7164-7168.

Research output: Contribution to journalArticle

Pelley, R. J. ; Maihle, Nita Jane ; Boerkoel, C. ; Shu, H. K. ; Carter, T. H. ; Moscovici, C. ; Kung, H. J. / Disease tropism of c-erbB : Effects of carboxyl-terminal tyrosine and internal mutations on tissue-specific transformation. In: Proceedings of the National Academy of Sciences of the United States of America. 1989 ; Vol. 86, No. 18. pp. 7164-7168.
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