Tyrosine kinase activity of the EGF receptor is enhanced by the expression of oncogenic 70Z-Cbl (original) (raw)

Oncogene volume 15, pages 2909–2919 (1997)Cite this article

Abstract

The 120 kD product of the c-Cbl oncogene is a prominent substrate of protein tyrosine kinases that lacks a known catalytic activity but possesses an array of binding sites for cytoplasmic signalling proteins. An oncogenic form of Cbl was recently identified in the 70Z/3 pre-B cell lymphoma which has a small deletion at the N-terminus of the Ring finger domain. This form of Cbl, termed 70Z-Cbl, exhibits an enhanced level of tyrosine phosphorylation compared with c-Cbl. Here we demonstrate that the expression of 70Z-Cbl induces a tenfold enhancement in the kinase activity of the EGF receptor in serum-starved and EGF-stimulated cells. In serum-starved cells this results in EGF receptor autophosphorylation and the recruitment of Grb2, Shc and Sos1 but does not induce a corresponding increase in MAP kinase activity. Furthermore the expression of 70Z-Cbl greatly enhances EGF-induced tyrosine phosphorylation of the protein tyrosine phosphatase SHP-2. We also show that the Cbl/EGF receptor complex is predominantly associated with CrkII and is distinct to the Grb2/Shc/Sos1 complex that associates with the EGF receptor. These findings therefore demonstrate a biochemical effect of an oncogenic Cbl protein and support predictions from C. elegans that Cbl functions as regulator of receptor tyrosine kinases.

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Authors and Affiliations

  1. Department of Pathology, The University of Western Australia, Queen Elizabeth II Medical Centre, Nedlands, 6907, Western Australia, Australia
    Christine BF Thien & Wallace Y Langdon

Authors

  1. Christine BF Thien
  2. Wallace Y Langdon

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Thien, C., Langdon, W. Tyrosine kinase activity of the EGF receptor is enhanced by the expression of oncogenic 70Z-Cbl.Oncogene 15, 2909–2919 (1997). https://doi.org/10.1038/sj.onc.1201468

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