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BCR/ABL-induced leukemogenesis causes phosphorylation of Hef1 and its association with Crkl.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Jong, Ron De Wijk, Atie Van Haataja, Leena Heisterkamp, Nora Groffen, John |
| Copyright Year | 1997 |
| Abstract | BCR/ABL is considered responsible for the development of Philadelphia chromosome-positive leukemia. Experimental animal models, such as transgenic mice, have demonstrated unambiguously that Bcr/Abl is capable of inducing leukemogenesis. The adaptor molecule Crkl is a major in vivo substrate of the deregulated Bcr/Abl tyrosine kinase and functions as a molecular link with other signaling proteins. While associated in vivo with Bcr/Abl through its SH3 domain, Crkl can interact simultaneously via its SH2 domain with other tyrosine-phosphorylated proteins. Here we report the identification of prominently tyrosine-phosphorylated proteins with a molecular mass of approximately 110 kDa, which bind specifically to the Crkl SH2 domain in leukemic tissues of P190BCR/ABL transgenic mice. We demonstrate that these proteins are identical to Hef1/Cas-L, which is related to p130(Cas). The proto-oncoprotein p120(Cbl) and Hef1, but not p130(Cas), were detectably phosphorylated on tyrosine in P190Bcr/Abl-expressing leukemic cells and were found in complex with Crkl, showing the existence of protein complexes in P190Bcr/Abl leukemic cells, consisting of P190Bcr/Abl, Crkl, and Hef1 or p120(Cbl). This supports a model in which Crkl acts as mediator between Bcr/Abl and downstream effectors. Since Hef1 is involved in the beta1-integrin signaling pathway, our study demonstrates that Bcr/Abl could specifically interfere with normal beta1-integrin signaling. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.jbc.org/content/272/51/32649.full.pdf |
| PubMed reference number | 9405482v1 |
| Volume Number | 272 |
| Issue Number | 51 |
| Journal | The Journal of biological chemistry |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Abetalipoproteinemia Animal Model B-Cell Receptor Complex BCR protein, human Biospecimen Core Resource Facility Body tissue CRKL protein Deregulation Fusion Proteins, bcr-abl Leukemogenesis Mediator brand of benfluorex hydrochloride Molecular Mass NEDD9 wt Allele Neuritis, Autoimmune, Experimental Oncogene Proteins Philadelphia Chromosome Protein Tyrosine Kinase SH2 Domain Signal Transduction Pathways abl Oncogene erbB-2 Receptor leukemia |
| Content Type | Text |
| Resource Type | Article |
