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Role of the tyrosine phosphatase SHP-1 in K562 cell differentiation

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Abstract

The erythro-megakaryoblastic leukemia cell line K562 undergoes erythroid or myeloid differentiation in response to treatment with various inducing agents. We observed that expression of the SH2-containing protein tyrosine phosphatase SHP-1 was induced upon exposure of K562 cells to differentiating agents. Under the same conditions, expression of SHP-2, a close relative of SHP-1, and the more distantly related PTP-1B remained unchanged. Induction of SHP-1 expression correlates with dephosphorylation of a specific and limited set of tyrosyl phosphoproteins, suggesting that dephosphorylation of these proteins may be important for the differentiation process. Importantly, expression of exogenous SHP-1 inhibits K562 proliferation and alters the adhesion properties of these cells, indicating a more differentiated phenotype. Moreover, SHP-1 is found in a complex with both p210 Bcr-Abl and p190 Bcr-Abl, suggesting that it may regulate Bcr-Abl or Bcr-Abl-associated phosphotyrosyl proteins. Our results indicate that induction of SHP-1 expression is important for K562 differentiation in response to various inducers and raise the possibility that functional inactivation of SHP-1 may play a role in progression to blast crisis in chronic myelogenous leukemia.

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Acknowledgements

This work was supported by P01 DK50654 to BGN and JDG. B Bruecher-Encke was supported by a post-doctoral fellowship from Deutsche Krebshilfe, Mildred Scheel Stiftung.

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  1. B Bruecher-Encke

    Present address: Department of Internal Medicine V, University of Heidelberg, Heidelberg, D-69115, Germany

Authors and Affiliations

  1. Division of Hematology-Oncology, Department of Medicine, Cancer Biology Program, Beth Israel-Deaconess Medical Center, Boston, MA, USA

    B Bruecher-Encke & BG Neel

  2. Division of Hematological Malignancies, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA

    JD Griffin

  3. Department of Microbiology, University of Virginia, Charlottesville, VA, USA

    U Lorenz

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  1. B Bruecher-Encke
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  4. U Lorenz
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Bruecher-Encke, B., Griffin, J., Neel, B. et al. Role of the tyrosine phosphatase SHP-1 in K562 cell differentiation. Leukemia 15, 1424–1432 (2001). https://doi.org/10.1038/sj.leu.2402214

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  • DOI: https://doi.org/10.1038/sj.leu.2402214

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