EGF receptor binding and transformation by v-cbl is ablated by the introduction of a loss-of-function mutation from the Caenorhabditis elegans sli-1 gene

Oncogene. 1997 May 8;14(18):2239-49. doi: 10.1038/sj.onc.1201193.


The 120 kD product of the c-cbl oncogene is rapidly tyrosine phosphorylated and recruited to the EGF receptor following ligand binding. Cbl's oncogenic potential is activated by a large carboxy-terminal truncation that generated v-cbl and removes the Ring finger and proline-rich SH3-binding domains. Here we show that this truncation reveals a novel and highly conserved domain that can interact directly with the EGF receptor in a phosphorylation dependent manner. Furthermore we demonstrate that the v-cbl domain is not utilized by c-cbl for recruitment to the receptor since this binding property is not evident in c-cbl constructs with proline domain deletions, and it is only revealed following deletion of the Ring finger. We also analyse a loss-of-function mutation from the C. elegans homologue, sli-1, and show that the corresponding mutation in v-cbl ablates transformation and EGF receptor association. Thus our findings provide further evidence that v-cbl possesses a novel and evolutionarily conserved phosphotyrosine binding domain and that the dual capability of EGF receptor binding by cbl involves two distinct mechanisms. In addition these findings raise the possibility that v-cbl may transform by competing with c-cbl for phosphorylated binding sites on activated receptor complexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells / metabolism
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans Proteins*
  • Cell Transformation, Neoplastic / genetics*
  • Conserved Sequence
  • Epidermal Growth Factor / pharmacology
  • ErbB Receptors / metabolism*
  • Helminth Proteins / genetics*
  • Mice
  • Mutation*
  • Oncogene Protein v-cbl
  • Phosphorylation / drug effects
  • Proline / chemistry
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-cbl
  • Rabbits
  • Retroviridae Proteins, Oncogenic / drug effects
  • Retroviridae Proteins, Oncogenic / genetics*
  • Retroviridae Proteins, Oncogenic / metabolism
  • Tyrosine / metabolism
  • Ubiquitin-Protein Ligases*


  • Caenorhabditis elegans Proteins
  • Helminth Proteins
  • Oncogene Protein v-cbl
  • Proto-Oncogene Proteins
  • Retroviridae Proteins, Oncogenic
  • Sli-1 protein, C elegans
  • Tyrosine
  • Epidermal Growth Factor
  • Proline
  • Proto-Oncogene Proteins c-cbl
  • Ubiquitin-Protein Ligases
  • ErbB Receptors
  • Cbl protein, mouse