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  • A dual role for the N-terminal domain of the IL-3 receptor in cell signalling.

A dual role for the N-terminal domain of the IL-3 receptor in cell signalling.

Nature communications (2018-01-28)
Sophie E Broughton, Timothy R Hercus, Tracy L Nero, Winnie L Kan, Emma F Barry, Mara Dottore, Karen S Cheung Tung Shing, Craig J Morton, Urmi Dhagat, Matthew P Hardy, Nicholas J Wilson, Matthew T Downton, Christine Schieber, Timothy P Hughes, Angel F Lopez, Michael W Parker
ABSTRACT

The interleukin-3 (IL-3) receptor is a cell-surface heterodimer that links the haemopoietic, vascular and immune systems and is overexpressed in acute and chronic myeloid leukaemia progenitor cells. It belongs to the type I cytokine receptor family in which the α-subunits consist of two fibronectin III-like domains that bind cytokine, and a third, evolutionarily unrelated and topologically conserved, N-terminal domain (NTD) with unknown function. Here we show by crystallography that, while the NTD of IL3Rα is highly mobile in the presence of IL-3, it becomes surprisingly rigid in the presence of IL-3 K116W. Mutagenesis, biochemical and functional studies show that the NTD of IL3Rα regulates IL-3 binding and signalling and reveal an unexpected role in preventing spontaneous receptor dimerisation. Our work identifies a dual role for the NTD in this cytokine receptor family, protecting against inappropriate signalling and dynamically regulating cytokine receptor binding and function.

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Monoclonal ANTI-FLAG® M2-Peroxidase (HRP) antibody produced in mouse, clone M2, purified immunoglobulin, buffered aqueous glycerol solution
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