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A novel MPL point mutation resulting in thrombopoietin-independent activation

Leukemia volume 16, pages 1500–1506 (2002)Cite this article

Abstract

Thrombopoietin (TPO) and its receptor (MPL) are important regulators of megakaryopoiesis. MPL belongs to a cytokine receptor superfamily. To date, all constitutively active MPL mutants have been artificially constructed with amino acid substitutions in the transmembrane domain or extracellular domain of the protein, and they activate signal transduction pathways in Ba/F3 cells that can also be activated by the normal MPL. In this paper, we report a novel spontaneously occurring mutation of MPL, with an amino acid substitution of Trp508 to Ser508 in the intracellular domain of MPL, that induces the factor-independent growth of Ba/F3 cells. Examination of intracellular signaling pathways demonstrated that the mutant MPL protein constitutively activates three distinct signaling pathways, SHC-Ras-Raf-MAPK/JNK, JAK-STAT, and PI3K-Akt-Bad.

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Acknowledgements

We thank Dr Takeshi Watanabe (Kyushu University) and Dr Daisuke Kitamura (Science University of Tokyo) for their helpful comments.

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Authors and Affiliations

  1. Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co Ltd, Tsukuba, Japan

    M Abe, K Suzuki, O Inagaki & H Shikama

  2. Institute for Project Coordination Department, Yamanouchi Pharmaceutical Co. Ltd, Tsukuba, Japan

    S Sassa

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Abe, M., Suzuki, K., Inagaki, O. et al. A novel MPL point mutation resulting in thrombopoietin-independent activation. Leukemia 16, 1500–1506 (2002). https://doi.org/10.1038/sj.leu.2402554

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