Epidermal Growth Factor Receptor Cytoplasmic Domain Mutations Trigger Ligand-Independent Transformation

Sharon Massoglia, Alane Gray, Thomas J. Dull, Susan Munemitsu, Hsing Jien Kung, Joseph Schlessinger, Axel Ullrich

研究成果: 雜誌貢獻文章同行評審

19 引文 斯高帕斯(Scopus)

摘要

The transforming gene product of avian erythroblastosis virus, v-erbB, is derived from the epidermal growth factor (EGF) receptor but has lost its extracellular ligand-binding domain and was mutated in its cytoplasmic portion, which is thought to be responsible for biological signal generation. We have repaired the deletion of extracellular EGF-binding sequences and investigated the functional consequences of cytoplasmic erbB mutations. Within the resulting EGF receptors, the autophosphorylation activities of the cytoplasmic domains of v-erbB-H and v-erbB-ES4 were fully ligand dependent in intact cells. However, the mitogenic and transforming signaling activities of an EGF receptor carrying v-erbB-ES4 (but not v-erbB-H) cytoplasmic sequences remained ligand independent, whereas those of a receptor with a v-erbB-H cytoplasmic domain were regulated by EGF or transforming growth factor α. Thus, structural alterations in the cytoplasmic domain of growth factor receptor tyrosine kinases may induce constitutive signaling activity without autophosphorylation. These findings provide new insight into the mechanism of receptor-mediated signal transduction and suggest a novel alternative for subversion of cellular control mechanisms and proto-oncogene activation.
原文英語
頁(從 - 到)3048-3055
頁數8
期刊Molecular and Cellular Biology
10
發行號6
DOIs
出版狀態已發佈 - 一月 1 1990
對外發佈

ASJC Scopus subject areas

  • 分子生物學
  • 細胞生物學

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