The DOI matches its OpenAlex record; 62 of the 62 references it cites were found in a registry or an index.
BCR-ABL-induced oncogenesis is mediated by direct interaction with the SH2 domain of the GRB-2 adaptor protein
Open accessAbstract
BCR-ABL is a chimeric oncoprotein that exhibits deregulated tyrosine kinase activity and is implicated in the pathogenesis of Philadelphia chromosome (Ph1)-positive human leukemias. Sequences within the first exon of BCR are required to activate the transforming potential of BCR-ABL. The SH2/SH3 domain-containing GRB-2 protein links tyrosine kinases to Ras signaling. We demonstrate that BCR-ABL exists in a complex with GRB-2 in vivo. Binding of GRB-2 to BCR-ABL is mediated by the direct interaction of the GRB-2 SH2 domain with a phosphorylated tyrosine, Y177, within the BCR first exon. The BCR-ABL-GRB-2 interaction is required for activation of the Ras signaling pathway. Mutation of Y177 to phenylalanine (Y177F) abolishes GRB-2 binding and abrogates BCR-ABL-induced Ras activation. The BCR-ABL (Y177F) mutant is unable to transform primary bone marrow cultures and is impaired in its ability to transform Rat1 fibroblasts. These findings implicate activation of Ras function as an important component in BCR-ABL-mediated transformation and demonstrate that GRB-2 not only functions in normal development and mitogenesis but also plays a role in oncogenesis.
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Cites
SH2 domains recognize specific phosphopeptide sequences
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Cited by
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Metadata
- Authors
- Pendergast, A. M., Quilliam, L. A., Cripe, L. D., Bassing, C. H., Dai, Z., Li, N., Batzer, A., Rabun, K. M., Der, C. J., Schlessinger, J., & Gishizky, M. L.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1993-10
- Volume
- 75
- Issue
- 1
- Pages
- 175-185
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2133124453
- Cited by
- 659
- References
- 62
- FWCI
- 27.98
- Type
- journal article
- Language
- en
- Open access
- hybrid
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- creativecommons.org/licenses/by-nc-nd/4.0/ (vor, 5131 d)
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- Pendergast, A. M., Quilliam, L. A., Cripe, L. D., Bassing, C. H., Dai, Z., Li, N., Batzer, A., Rabun, K. M., Der, C. J., Schlessinger, J., & Gishizky, M. L. (1993). BCR-ABL-induced oncogenesis is mediated by direct interaction with the SH2 domain of the GRB-2 adaptor protein. Cell. https://doi.org/10.1016/0092-8674(93)90689-n
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
