Disease tropism of c-erbB: Effects of carboxyl-terminal tyrosine and internal mutations on tissue-specific transformation

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

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18 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
頁(從 - 到)7164-7168
頁數5
期刊Proceedings of the National Academy of Sciences of the United States of America
86
發行號18
DOIs
出版狀態已發佈 - 一月 1 1989
對外發佈

ASJC Scopus subject areas

  • 多學科

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