Granulocyte-macrophage colony-stimulating factor receptors alter their binding characteristics during myeloid maturation through up-regulation of the affinity converting beta subunit (KH97)
| Autor: | L M, Budel, H, Hoogerbrugge, K, Pouwels, C, van Buitenen, R, Delwel, B, Löwenberg, I P, Touw |
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| Rok vydání: | 1993 |
| Předmět: |
Base Sequence
Transcription Genetic Macromolecular Substances Molecular Sequence Data Granulocyte-Macrophage Colony-Stimulating Factor Tretinoin Transfection Polymerase Chain Reaction Recombinant Proteins Cell Line Up-Regulation Kinetics Leukemia Promyelocytic Acute Oligodeoxyribonucleotides Leukemia Myeloid Receptors Granulocyte-Macrophage Colony-Stimulating Factor Leukemia Myelogenous Chronic BCR-ABL Positive Acute Disease Tumor Cells Cultured Animals Humans RNA Neoplasm Sequence Deletion |
| Zdroj: | The Journal of biological chemistry. 268(14) |
| ISSN: | 0021-9258 |
| Popis: | Acute myeloid leukemia blasts express dual affinity (high and low) granulocyte-macrophage colony-stimulating factor (GM-CSF) binding, and the high affinity GM-CSF binding is counteracted by excess interleukin-3 (IL-3). Neutrophils express a single class of GM-CSF-R with intermediate affinity that lack IL-3 cross-reactivity. Here we demonstrate the differentiation associated changes of GM-CSF binding characteristics in three models representative of different stages of myeloid maturation. We find that high affinity GM-CSF binding is converted into intermediate affinity binding, which still cross-reacts with IL-3, beyond the stage of promyelocytes. During terminal maturation towards neutrophils, IL-3 cross-reactivity is gradually lost. We sought to determine the mechanism underlying the affinity conversion of the GM-CSF-R. Northern and reverse transcriptase-polymerase chain reaction analysis of GM-CSF-R alpha and -beta c (KH97) transcripts did not provide indications for the involvement of GM-CSF-R splice variants in the formation of the intermediate affinity GM-CSFR complex. In COS-cell transfectants with increasing amounts of beta c in the presence of a fixed number of GM-CSF-R alpha chains, the high affinity GM-CSF binding converted into intermediate affinity GM-CSF binding. These results are discussed in view of the concept that increasing expression of beta c subunits may cause alternative oligomerization of the GM-CSF-R alpha and -beta c subunits resulting in the formation of intermediate rather than high affinity GM-CSFR alpha.beta c complexes. |
| Databáze: | OpenAIRE |
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