The two major sites of cbl tyrosine phosphorylation in abl-transformed cells select the crkL SH2 domain

Christopher E. Andoniou, Christine B.F. Thien, Wallace Y. Langdon

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103 Citations (Scopus)


We recently found that the 120-kD protein product of the c-cbl oncogene is tyrosine phosphorylated in tumor cells generated by bcr-abl or v-abl and that p120(cbl) will associate with these proteins in vivo. We also found an oncogenic form of cbl protein in the 70Z/3 pre-B cell lymphoma which exhibits deregulated tyrosine phosphorylation. These findings have led us to broaden our study of cbl's involvement in abl-mediated tumorigenesis. Here we show by immunodepletion that cbl is the major 120-kD tyrosine phosphorylated protein in cells which express activated forms of the abl oncogene. We also demonstrate that tyrosine phosphorylation of p120(cbl) in bcr-abl transformed cells does not alter its subcellular localization. In addition we show that the oncogenic 70Z/3 form of cbl exhibits enhanced tyrosine phosphorylation in v-abl infected cells and that cbl is heavily tyrosine phosphorylated in hemopoietic cells transformed by v-src. Finally this study identifies two sites that are essential for the tyrosine phosphorylation of cbl in abl-transformed cells. These sites conform to the preferred abl kinase substrate sequence of YXXP and we show that following phosphorylation they mediate an association with the crkL SH2 domain.

Original languageEnglish
Pages (from-to)1981-1989
Number of pages9
Issue number9
Publication statusPublished - 3 Jun 1996
Externally publishedYes


  • Cbl oncogene
  • Cell transformation
  • Crk adaptor
  • Tyrosine kinase

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