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  • Original Paper
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SHIP-mediated inhibition of K562 erythroid differentiation requires an intact catalytic domain and Shc binding site

Oncogene volume 18, pages 7135–7148 (1999)Cite this article

Abstract

Growing evidence supports a role for the SHIP inositol 5′-phosphatase in the negative regulation of a variety of receptor-mediated signaling pathways in hematopoietic cells. SHIP expression among cultured cell lines was examined and found to be restricted to cells of hematopoietic origin, with the exception of the K562 erythroleukemia cell line, in which SHIP protein and mRNA were undetectable. The absence of endogenous SHIP in K562 cells provided a useful system to study the role of SHIP in growth and differentiation. When stably expressed in K562 cells, SHIP was found to be constitutively tyrosine phosphorylated and associated with endogenous Shc and Grb-2. Stable expression of SHIP did not affect growth of the cells but resulted in decreased synthesis of hemoglobin protein and ε-globin mRNA in response to hemin, an inducer of erythroid differentiation. This effect was not due to increased cell death in the SHIP-expressing lines following hemin stimulation, but was likely the result of an impaired differentiation program in these cells. Mutational analysis indicated that SHIP must retain both an intact catalytic domain and Shc binding site to efficiently inhibit K562 erythroid differentiation.

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Acknowledgements

We thank William Muller and Brian Leber for critical reading of this manuscript. We thank Brian Allore for the automated sequencing data and Dinsdale Gooden for oligonucleotide synthesis (The Central Facility of the Institute for Molecular Biology and Biotechnology, McMaster University). This work was supported by a grant to Peter Whyte from the Medical Research Council of Canada.

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  1. Institute for Molecular Biology and Biotechnology, McMaster University, 1200 Main Street West, Hamilton, L8N 3Z5, Ontario, Canada

    Josie Siegel, Yun Li & Peter Whyte

  2. Department of Pathology and Molecular Medicine, McMaster University, 1200 Main Street West, Hamilton, L8N 3Z5, Ontario, Canada

    Josie Siegel, Yun Li & Peter Whyte

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Siegel, J., Li, Y. & Whyte, P. SHIP-mediated inhibition of K562 erythroid differentiation requires an intact catalytic domain and Shc binding site. Oncogene 18, 7135–7148 (1999). https://doi.org/10.1038/sj.onc.1203212

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