The product of the cbl oncogene forms stable complexes in vivo with endogenous Crk in a tyrosine phosphorylation-dependent manner
| Autor: | Andalan R. Saltiel, Vered Ribon, Susan Hubbell, Roman Herrera |
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| Rok vydání: | 1996 |
| Předmět: |
animal structures
T-Lymphocytes Ubiquitin-Protein Ligases Retroviridae Proteins Oncogenic Fusion Proteins bcr-abl Protein tyrosine phosphatase macromolecular substances SH2 domain environment and public health Proto-Oncogene Mas Receptor tyrosine kinase Cell Line src Homology Domains Adapter molecule crk chemistry.chemical_compound Mice Transformation Genetic hemic and lymphatic diseases Proto-Oncogene Proteins Proto-Oncogenes Tumor Cells Cultured Animals Humans Proto-Oncogene Proteins c-cbl Tyrosine Phosphorylation Oncogene Protein v-crk Molecular Biology Binding Sites biology Tyrosine phosphorylation Cell Biology 3T3 Cells Cell biology chemistry embryonic structures biology.protein Proto-oncogene tyrosine-protein kinase Src Research Article |
| Zdroj: | Molecular and cellular biology. 16(1) |
| ISSN: | 0270-7306 |
| Popis: | The cellular homologs of the v-Crk oncogene product are composed exclusively of Src homology region 2 (SH2) and SH3 domains. v-Crk overexpression in fibroblasts causes cell transformation and elevated tyrosine phosphorylation of specific cellular proteins. Among these proteins is a 130-kDa protein, identified as p130cas, that forms a stable complex in vivo with v-Crk. We have explored the role of endogenous Crk proteins in Bcr-Abl-transformed cells. In the K562 human chronic myelogenous leukemia cell line, p130cas is not tyrosine phosphorylated or bound to Crk. Instead, Crk proteins predominantly associate with the tyrosine-phosphorylated proto-oncogene product of Cbl. In vitro analysis showed that this interaction is mediated by the SH2 domain of Crk and can be inhibited with a phosphopeptide containing the Crk-SH2 binding motif. In NIH 3T3 cells transformed by Bcr-Abl, c-Cbl becomes strongly tyrosine phosphorylated and associates with c-Crk. The complex between c-Crk and c-Cbl is also seen upon T-cell receptor cross-linking or with the transforming, tyrosine-phosphorylated c-Cbl. These results indicate that Crk binds to c-Cbl in a tyrosine phosphorylation-dependent manner, suggesting a physiological role for the Crk-c-Cbl complex in Bcr-Abl tyrosine phosphorylation-mediated transformation. |
| Databáze: | OpenAIRE |
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