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

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.Sophie E. Broughton, Timothy R. Hercus, Tracy L. Nero, Winnie L. Kan ... Timothy P. Hughes, Angel F. Lopez ... et al

"Now I know the terrain": phenomenological exploration of CFTs learning on evidence-based practice

Couple and family therapists are rarely the focus of research yet are critical for positive outcomes in therapy. The attempts to integrate evidence-based approaches into the practice of couple and family therapy have been controversial resulting in passionate and at times divisive dialogue. The aims of this research project were to explore what do couple and family therapists experience when learning an evidence-based approach to working with couples and families. A total of 14 couple and family therapists were interviewed about their experience with learning an evidence-based approach. The research was guided methodologically by interpretive phenomenological analysis. Three themes emerged from the participants’ experiences including: the supports and challenges in learning; the embodiment of a therapy practice; and the experience of shame while learning