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Cytokines and Cell Signaling

The SH2 domain-containing protein tyrosine phosphatase SHP-1 is induced by granulocyte colony-stimulating factor (G-CSF) and modulates signaling from the G-CSF receptor

Leukemia volume 14, pages 1284–1291 (2000)Cite this article

Abstract

The SH2 domain-containing protein tyrosine phosphatase SHP-1 is expressed widely in the hematopoietic system. SHP-1 has been shown to negatively control signal transduction from many cytokine receptors by direct docking to either the receptor itself, or to members of the Jak family of tyrosine kinases which are themselves part of the receptor complex. Motheaten and viable motheaten mice, which are deficient in SHP-1, have increased myelopoiesis and show an accumulation of morphologically and phenotypically immature granulocytes, suggesting a role for SHP-1 in granulocytic differentiation. Here, we report that SHP-1 protein levels are up-regulated during the granulocyte colony-stimulating factor (G-CSF)-mediated granulocytic differentiation of myeloid 32D cells. Enforced expression of SHP-1 in these cells leads to decreased proliferation and enhanced differentiation, while introduction of a catalytically inactive mutant produces increased proliferation and results in a delay of differentiation. In vitro binding revealed that the SH2 domains of SHP-1 are unable to associate directly with tyrosine-phosphorylated G-CSF receptor (G-CSF-R). Furthermore, over-expression of SHP-1 in Ba/F3 cells expressing a G-CSF-R mutant lacking all cytoplasmic tyrosines also inhibited proliferation. Together, these data suggest that SHP-1 directly modulates G-CSF-mediated responses in hematopoietic cells via a mechanism that does not require docking to the activated G-CSF-R.

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Acknowledgements

We thank Karola van Rooyen for her outstanding graphical work. This work was supported by an EMBO Long Term Fellowship (ACW), grants CA79891 and GM58893 from the NIH (TY), and funding from the NWO and Dutch Cancer Society.

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  1. L Smith

    Present address: Department of Medicine, Centre for Immunology, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia

Authors and Affiliations

  1. Institute of Hematology, Erasmus University Rotterdam, Rotterdam, The Netherlands

    AC Ward, SPMA Oomen, J Gits, AA Soede-Bobok & CAJ Erpelinck-Verschueren

  2. Department of Hematology, Dr Daniel den Hoed Cancer Center, Rotterdam, The Netherlands

    L Smith, D van Leeuwen & IP Touw

  3. Department of Cancer Biology, The Cleveland Clinic Foundation Research Institute, Cleveland, Ohio, USA

    T Yi

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Ward, A., Oomen, S., Smith, L. et al. The SH2 domain-containing protein tyrosine phosphatase SHP-1 is induced by granulocyte colony-stimulating factor (G-CSF) and modulates signaling from the G-CSF receptor. Leukemia 14, 1284–1291 (2000). https://doi.org/10.1038/sj.leu.2401822

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