Coupling of the proto-oncogene product c-Cbl to the epidermal growth factor receptor
Meisner, Herman ; Czech, Michael P.
Citations
Authors
Student Authors
Faculty Advisor
Academic Program
UMass Chan Affiliations
Document Type
Publication Date
Keywords
Amino Acid Sequence
Cell Line
GRB2 Adaptor Protein
Humans
Immunoblotting
Molecular Sequence Data
Peptides
Phosphorylation
Precipitin Tests
Proline
Protein Binding
Proteins
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-cbl
Receptor, Epidermal Growth Factor
*Signal Transduction
Tissue Distribution
Tyrosine
*Ubiquitin-Protein Ligases
Life Sciences
Medicine and Health Sciences
Subject Area
Embargo Expiration Date
Link to Full Text
Abstract
The proto-oncogene product, Cbl, is a 120-kDa protein present in lymphocytes that contains numerous PXXP motifs in its COOH-terminal region and constitutively binds the SH3-containing adaptor protein Grb2. Cross-linking of CD3 and CD4 receptors in Jurkat T cells causes tyrosine phosphorylation of Cbl and its association with phosphatidylinositol 3'-kinase (Meisner, H., Conway, B., Hartley, D., and Czech, M. P. (1995) Mol. Cell. Biol. 15, 3571-3578). Here we demonstrate that Cbl is also present in nonlymphoid cells, and that epidermal growth factor (EGF) elicits its rapid tyrosine phosphorylation in human embryonic 293 cells. Immunoprecipitates of Cbl from lysates of these cells contain Grb2 in the basal state, while EGF stimulation causes co-precipitation of tyrosine-phosphorylated EGF receptors. Similarly, EGF receptor immunoprecipitates from EGF-treated 293 cells contain Cbl and Grb2. Both Grb2 and EGF receptors are released from Cbl in the presence of a proline-rich peptide that binds the NH2-terminal SH3 domain of Grb2. These results indicate that autophosphorylated EGF receptors associate with the SH2 domain of Grb2, which is complexed through its SH3 domain with proline-rich regions of Cbl. Such recruitment of Cbl to EGF receptors may reflect an important mechanism for its tyrosine phosphorylation and for assembling signaling components that mediate or modulate EGF actions.
Source
J Biol Chem. 1995 Oct 27;270(43):25332-5.