Abstract
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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Thien, C., Langdon, W. 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 14, 2239–2249 (1997). https://doi.org/10.1038/sj.onc.1201193
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1201193
Keywords
This article is cited by
-
Serine mutations that abrogate ligand-induced ubiquitination and internalization of the EGF receptor do not affect c-Cbl association with the receptor
Oncogene (2003)
-
Beyond the RING: CBL proteins as multivalent adapters
Oncogene (2001)
-
Cbl: many adaptations to regulate protein tyrosine kinases
Nature Reviews Molecular Cell Biology (2001)
-
A Drosophila analogue of v-Cbl is a dominant-negative oncoprotein in vivo
Oncogene (2000)
-
Structure of the amino-terminal domain of Cbl complexed to its binding site on ZAP-70 kinase
Nature (1999)