Granulocyte-macrophage colony-stimulating factor and interleukin-3 induce rapid phosphorylation and activation of the proto-oncogene Raf-1 in a human factor-dependent myeloid cell line.

作者: Y Kanakura , B Druker , KW Wood , HJ Mamon , K Okuda

DOI: 10.1182/BLOOD.V77.2.243.243

关键词: Cancer researchGRB2Cell surface receptorReceptor tyrosine kinasePhosphorylation cascadeCell biologyBiologyProtein phosphorylationPlatelet-derived growth factor receptorProtein tyrosine phosphataseMAP2K7

摘要: RANULOCYTE-MACROPHAGE colony-stimulatG ing factor (GM-CSF) and interleukin-3 (IL-3) are members of a family growth factors that stimulate the proliferation, differentiation, function hematopoietic ~e1ls.l’~ The action both is known to be mediated through binding specific, high-affinity, cell surface receptors. However, postreceptor signal transduction pathways largely unknown. In human murine myeloid lines, GM-CSF IL-3 have been shown protein tyrosine kinase activity resulting in rapid phosphorylation several unidentified membrane cytoplasmic proteins?” For example, we previously activate factor-dependent megakaryoblastic line, M07, substrates apparent Mr = 150,000, 125,000, 93,000, 70,000, 55,000, 42,000, 36,000.12 Identification these likely important elucidating mechanism transduction. preliminary experiments, noted 70-Kd observed after or treatment M07 cells comigrated with product c-raf-1 protooncogene, Raf-1. 3T3 fibroblasts, Raf-1 has rapidly phosphorylated on serine response platelet-derived factor.I3 itself serinehhreonine kinase, its may activated by some ~ituations,’~,~~ suggesting common intermediate step from Therefore, examined expression state stimulation.

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