Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Gale, R.E. et al.

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.

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-3 (IL-3), and IL-5 (GMRbetaC) 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 (betaIT) has a predicted tail of 46 amino acids, instead of 432 for betaC, with 23 amino acids in common with betaC and then a new sequence of 23 amino acids. In primary myeloid cells, betaIT 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-betaIT antibodies demonstrated its presence in primary myeloid cells and cell lines. Coexpression of betaIT converted low-affinity GMRalpha chains (KD 2.5 nmol/L) to higher-affinity alphabeta complexes (KD 200 pmol/L). These could bind JAK2 that was tyrosine- phosphorylated by stimulation with GM-CSF. betaIT did not support GM-CSF-induced proliferation when cotransfected with GMRalpha into CTLL-2 cells. Therefore, it may interfere with the signal-transducing properties of the betaC chain and play a role in the pathogenesis of leukemia.[1]

References

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, R.E., Freeburn, R.W., Khwaja, A., Chopra, R., Linch, D.C. Blood (1998) [Pubmed]

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