Suppressor of cytokine signalling (SOCS) proteins form part of a classical negative feedback system that regulates cytokine signal transduction. SOCS5 inhibits the IL4 signaling pathway, which promotes the Th (helper T) 2 cell development []. SOCS5 and SOCS4 regulate epidermal growth factor receptor signaling [].
This entry represents interleukin-5 (IL5), also known as eosinophil differentiation factor (EDF),is a lineage-specific cytokine for eosinophilpoiesis [, ]. It regulates eosinophil growth and activation [], and thus plays an important role indiseases associated with increased levels of eosinophils, including asthma[]. IL5 has a similar overall fold to other cytokines (e.g., IL2, IL4 and GCSF)[], but while these exist as monomeric structures, IL5 is a homodimer. Thefold contains an anti-parallel 4-α-helix bundle with a left handed twist,connected by a 2-stranded anti-parallel β-sheet [, ]. The monomers areheld together by 2 interchain disulphide bonds [].
This entry represents the SOCS box domain of SOCS5.Suppressor of cytokine signalling (SOCS) proteins form part of a classical negative feedback system that regulates cytokine signal transduction. SOCS5 inhibits the IL4 signaling pathway, which promotes the Th (helper T) 2 cell development []. SOCS5 and SOCS4 regulate epidermal growth factor receptor signaling [].The general function of the SOCS box is the recruitment of the ubiquitin-transferase system. The SOCS box interacts with Elongins B and C, Cullin-5 or Cullin-2, Rbx-1, and E2. Therefore, SOCS-box-containing proteins probably function as E3 ubiquitin ligases and mediate the degradation of proteins associated through their N-terminal regions [, ].
T-Lymphocytes regulate the growth and differentiation of certain lymphopoietic andhaemopoietic cells through the release of various secreted protein factors [].These factors, which include interleukin-2 (IL2), are secreted by lectin- or antigen-stimulatedT-cells, and have various physiological effects. IL2 is a lymphokine that induces theproliferation of responsive T-cells. In addition, it acts on some B-cells, via receptor-specificbinding [], as a growth factor and antibody production stimulant []. Theprotein is secreted as a single glycosylated polypeptide, and cleavage of a signal sequenceis required for its activity []. Solution NMR suggests that the structure of IL2 comprises abundle of 4 helices (termed A-D), flanked by 2 shorter helices and several poorly-definedloops. Residues in helix A, and in the loop region between helices A and B, are important forreceptor binding. Secondary structure analysis has suggested similarity to IL4 and granulocyte-macrophage colony stimulating factor (GMCSF) [].
