SOCS2 Can Enhance Interleukin-2 (IL-2) and IL-3 Signalling by Accelerating SOCS3 Degradation

Cytokine responses can be regulated by a family of proteins termed suppressors of cytokine signaling (SOCS) which can inhibit the JAK/STAT pathway in a classical negative-feedback manner. While the SOCS are thought to target signaling intermediates for degradation, relatively little is known about how their turnover is regulated. Unlike other SOCS family members, we find that SOCS2 can enhance interleukin-2 (IL-2)- and IL-3-induced STAT phosphorylation following and potentiate proliferation in response to cytokine stimulation. As a clear mechanism for these effects, we demonstrate that expression of SOCS2 results in marked proteasome-dependent reduction of SOCS3 and SOCS1 protein expression. Furthermore, we provide evidence that this degradation is dependent on the presence of an intact SOCS box and that the loss of SOCS3 is enhanced by coexpression of elongin B/C. This suggests that SOCS2 can bind to SOCS3 and elongin B/C to form an E3 ligase complex resulting in the degradation of SOCS3. Therefore, SOCS2 can enhance cytokine responses by accelerating proteasome-dependent turnover of SOCS3, suggesting a mechanism for the gigantism observed in SOCS2 transgenic mice.

Compressive membrane action in composite floor slabs in the Cardington LBTF

This paper presents the results of an experimental study (the ultimate load capacity of composite metal decking/concrete floor slabs. Full-scale in situ testing of composite floor slabs was carried out in the Building Research Establishment's Large Building Test Facility (LBTF) at Cardington. A parallel laboratory test programme, which compared the behaviour of composite floor slabs strips, also carried out at Queen's University Belfast (QUB). Articular attention was paid to the contribution of compressive membrane action to the load carrying capacity. The results of both test programmes were compared with predictions by yield line theory and a theoretical prediction method in which the amount of horizontal restraint mid be assessed. The full-scale tests clearly demon-wed the significant contribution of compressive membrane effects to the load capacity of interior floor panels with a lesser contribution to edge/corner panels.