SH2-containing phosphotyrosine phosphatase SHP-1 is involved in BCR-ABL signal transduction pathways

  • Authors:
    • T Tauchi
    • K Ohyashiki
    • Y Yamashita
    • S Sugimoto
    • K Toyama
  • View Affiliations

  • Published online on: September 1, 1997     https://doi.org/10.3892/ijo.11.3.471
  • Pages: 471-475
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Abstract

The BCR-ABL fusion protein is strongly implicated in the malignant process of Philadelphia (Ph-1)-positive leukemia. The BCR-ABL fusion protein exhibits a deregulated tyrosine kinase activity capable of phosphorylating different cellular substrates in vivo and in vitro. SHP-1 (SHPTP1, PTP1C, HCP, SHP) is an SH2 domain-containing tyrosine phosphatase expressed predominantly in hematopoietic cells. The association of the murine motheaten phenotype of severe hematopoietic dysregulation with loss of SHP-1 tyrosine phosphatase activity indicates a critical role of SHP-1 in the regulation of hematopoietic cell growth and differentiation. Experiments were performed to determine whether SHP-1 might form specific complexes with BCR-ABL signaling pathway. We found that SHP-1 was highly and constitutively tyrosine phosphorylated in 32DCl3 and TF-1 cells transfected with BCR-ABL expression vector. Furthermore, SHP-1 and BCR-ABL formed stable complexes in BCR-ABL expressing cells. Direct binding between SHP-1 and Grb2 was observed in vitro. Expression of BCR-ABL in TF-1 cells resulted in a two-fold increase in SHP-1 phosphatase activity. BCR-ABL tyrosine kinase was able to phosphorylate recombinant SHP-1 protein in vitro. SHP-1 therefore has the capacity to bind and potentially modulate the signaling effectors involved in activation of Ras, and accordingly, regulation of cellular transformation of BCR-ABL.

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September 1997
Volume 11 Issue 3

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

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Spandidos Publications style
Tauchi T, Ohyashiki K, Yamashita Y, Sugimoto S and Toyama K: SH2-containing phosphotyrosine phosphatase SHP-1 is involved in BCR-ABL signal transduction pathways. Int J Oncol 11: 471-475, 1997
APA
Tauchi, T., Ohyashiki, K., Yamashita, Y., Sugimoto, S., & Toyama, K. (1997). SH2-containing phosphotyrosine phosphatase SHP-1 is involved in BCR-ABL signal transduction pathways. International Journal of Oncology, 11, 471-475. https://doi.org/10.3892/ijo.11.3.471
MLA
Tauchi, T., Ohyashiki, K., Yamashita, Y., Sugimoto, S., Toyama, K."SH2-containing phosphotyrosine phosphatase SHP-1 is involved in BCR-ABL signal transduction pathways". International Journal of Oncology 11.3 (1997): 471-475.
Chicago
Tauchi, T., Ohyashiki, K., Yamashita, Y., Sugimoto, S., Toyama, K."SH2-containing phosphotyrosine phosphatase SHP-1 is involved in BCR-ABL signal transduction pathways". International Journal of Oncology 11, no. 3 (1997): 471-475. https://doi.org/10.3892/ijo.11.3.471