The tetramerization domain-independent Ras activation by BCR-ABL oncoprotein in hematopoietic cells.

  • Authors:
    • T Tauchi
    • S Okabe
    • K Miyazawa
    • K Ohyashiki
  • View Affiliations

  • Published online on: June 1, 1998     https://doi.org/10.3892/ijo.12.6.1269
  • Pages: 1269-1345
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Abstract

BCR-ABL is a chimeric oncoprotein that exhibits deregulated tyrosine kinase activity and is implicated in the pathogenesis of Philadelphia chromosome-positive human leukemias. We have previously shown that BCR-ABL activates Ras signaling pathways required for transformation. To elucidate the mechanisms whereby BCR-ABL induced transformation in hematopoietic cells, we examined the biological effects of expression of a series of BCR-ABL mutants. We found that the Grb2 binding site-deleted BCR-ABL and the SH2 domain-deleted BCR-ABL, as well as the tetramerization domain-deleted BCR-ABL do not diminish the transforming properties of BCR-ABL in hematopoietic cells, although these mutations were previously shown to drastically reduce the transforming activity of BCR-ABL in fibroblasts. The tetramerization domain-deleted BCR-ABL did not induce tyrosine phosphorylation of CrkL, SHP-2, Vav and the interactions of BCR-ABL and Shc. However, Ras is activated, Shc is tyrosine phosphorylated and binds to Grb2 in the tetramerization domain-deleted BCR-ABL expressing hematopoietic cells. These results suggest that the tetramerization domain-independent Ras activation is mediated by Shc proteins and induces the transformation of hematopoietic cells.

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June 1998
Volume 12 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Tauchi, T., Okabe, S., Miyazawa, K., & Ohyashiki, K. (1998). The tetramerization domain-independent Ras activation by BCR-ABL oncoprotein in hematopoietic cells.. International Journal of Oncology, 12, 1269-1345. https://doi.org/10.3892/ijo.12.6.1269
MLA
Tauchi, T., Okabe, S., Miyazawa, K., Ohyashiki, K."The tetramerization domain-independent Ras activation by BCR-ABL oncoprotein in hematopoietic cells.". International Journal of Oncology 12.6 (1998): 1269-1345.
Chicago
Tauchi, T., Okabe, S., Miyazawa, K., Ohyashiki, K."The tetramerization domain-independent Ras activation by BCR-ABL oncoprotein in hematopoietic cells.". International Journal of Oncology 12, no. 6 (1998): 1269-1345. https://doi.org/10.3892/ijo.12.6.1269