1. A novel MPL point mutation resulting in thrombopoietin-independent activation.
- Author
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Abe, M., Suzuki, K., Inagaki, O, Sassa, S, and Shikama, H
- Subjects
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THROMBOPOIETIN , *HEMATOPOIETIC growth factors , *PROTEIN metabolism , *AMINO acids , *ANIMAL experimentation , *BIOCHEMISTRY , *CARRIER proteins , *CELL lines , *CELL receptors , *CELLULAR signal transduction , *COLONY-stimulating factors (Physiology) , *COMPARATIVE studies , *GENETIC techniques , *HEMATOPOIETIC stem cells , *PHENOMENOLOGY , *RESEARCH methodology , *MEDICAL cooperation , *MEMBRANE proteins , *MICE , *MILK proteins , *GENETIC mutation , *PHOSPHOTRANSFERASES , *PROTEIN-tyrosine kinases , *PROTEINS , *RECOMBINANT proteins , *RESEARCH , *TRANSFERASES , *DNA-binding proteins , *EVALUATION research - 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 Trp(508) to Ser(508) 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. [ABSTRACT FROM AUTHOR]
- Published
- 2002
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