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A truncated isoform of the human beta chain common to the receptors for granulocyte-macrophage colony-stimulating factor, interleukin-3 (IL-3), and IL-5 with increased mRNA expression in some patients with acute leukemia

Gale, RE; Freeburn, RW; Khwaja, A; Chopra, R; Linch, DC; (1998) A truncated isoform of the human beta chain common to the receptors for granulocyte-macrophage colony-stimulating factor, interleukin-3 (IL-3), and IL-5 with increased mRNA expression in some patients with acute leukemia. BLOOD , 91 (1) 54 - 63.

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Abstract

We report here a naturally occurring isoform of the human beta chain common to the receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 (IL-3), and IL-5 (GMR beta(C)) with a truncated intracytoplasmic tail caused by deletion of a 104-bp exon in the membrane-proximal region of the chain. This beta intracytoplasmic truncated chain (beta(IT)) has a predicted tail of 46 amino acids, instead of 432 for beta(C), with 23 amino acids in common with beta(C) and then a new sequence of 23 amino acids, In primary myeloid cells, beta(IT) comprised approximately 20% of the total beta chain message, but was increased up to 90% of total in blast cells from a significant proportion of patients with acute leukemia. Specific anti-beta(IT) antibodies demonstrated its presence in primary myeloid cells and cell lines. Coexpression of beta(IT) converted low-affinity GMR alpha chains (K-D 2.5 nmol/L) to higher-affinity alpha beta complexes (K-D 200 pmol/L). These could bind JAK2 that was tyrosine-phosphorylated by stimulation with GM-CSF. beta(IT) did not support GM-CSF-induced proliferation when cotransfected with GMR alpha into CTLL-2 cells, Therefore, it may interfere with the signal-transducing properties of the beta(C) chain and play a role in the pathogenesis of leukemia. (C) 1998 by The American Society of Hematology.

Type: Article
Title: A truncated isoform of the human beta chain common to the receptors for granulocyte-macrophage colony-stimulating factor, interleukin-3 (IL-3), and IL-5 with increased mRNA expression in some patients with acute leukemia
Keywords: GM-CSF RECEPTOR, DISTINCT CYTOPLASMIC REGIONS, ERYTHROPOIETIN RECEPTOR, ALPHA-SUBUNIT, HEMATOPOIETIC-CELLS, SIGNAL-TRANSDUCTION, MOLECULAR-CLONING, C-FOS, ACTIVATION, GENE
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: http://discovery.ucl.ac.uk/id/eprint/88613
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