SOCS proteins and inflammation
Small, secreted proteins called cytokines mediate regulation of the hematopoietic system and the immune response.
Cytokine signalling is initiated through interaction with specific trans-membrane receptor subunits. The subsequent receptor oligomerisation results in activation of either an intrinsic kinase domain or receptor associated JAK kinases, and the following cascade of intracellular phosphorylation and signal transduction culminates in an appropriate cellular response. This cascade requires exquisite cellular control and loss of regulation can promote tumorigenesis and chronic inflammation.
The expression of SOCS proteins can be induced by cytokine stimulation, and they serve to interfere with signalling not only from the inducing cytokine in a classic “negative-feedback” loop, but also to regulate signalling downstream of other cytokines, a process known as “cross-talk”.
Ubiquitination involves the transfer of a ubiquitin molecule via an E1-E2-E3 enzyme cascade, where the E3 ligase functions as both a substrate recognition molecule and a catalyst for the transfer of ubiquitin to a lysine in the substrate protein
We are interested in SOCS proteins and their role in inflammation.