Tumour induction by activated abl involves tyrosine phosphorylation of the product of the cbl oncogene

C. E. Andoniou, C. B F Thien, W. Y. Langdon

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214 Citations (Scopus)

Abstract

v-cbl is the transforming gene of a murine retrovirus which induces pre-B cell lymphomas and myelogenous leukaemias. It encodes 40 kDa of a gag fusion protein which is localized in the cytoplasm and nucleus of infected cells. The c-cbl oncogene encodes a 120 kDa cytoplasmic protein and its overexpression is not associated with tumorigenesis. The c-cbl sequence has shown that v-cbl was generated by a truncation that removed 60% of the C-terminus. In this study, we carried out experiments to identify the position within cbl where the transition occurs between non-tumorigenic and tumorigenic forms. These experiments focused attention on a region of 17 amino acids which is deleted from cbl in the 70Z/3 pre-B lymphoma due to a splice acceptor site mutation. This mutation activates cbl's tumorigenic potential and induces its tyrosine phosphorylation. We also show that the expression of the v-abl and bcr - abl oncogenes results in the induction of cbl tyrosine phosphorylation, and that abl and cbl associate in vivo. These findings demonstrate that tyrosine-phosphorylated cbl promotes tumorigenesis and that cbl is a downstream target of the bcr - abl and v-abl kinases.

Original languageEnglish
Pages (from-to)4415-4423
Number of pages9
JournalThe EMBO Journal
Volume13
Issue number19
Publication statusPublished - 1 Dec 1994
Externally publishedYes

Keywords

  • bcr-abl
  • cbl
  • Leukaemia
  • Lymphoma
  • Tyrosine kinase

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