Ring effectors

Our own experiments indicate that i.v. injection of Tregs is able to prevent CHS reactions, but the Tregs never entered the tissue site, i.e. the skin in which the allergic reaction takes place [36]. Rather, their suppressive action seems to be mediated by IL-10 and involves endothelial cells, as Ring et al. [36] have been shown that the adherence of effector T cells to inflamed vascular endothelium is blocked by Treg injections. Thus,... 

Ring S, Schafer SC, Mahnke K, Lehr HA, Enk AH CD4+ CD25+ regula- 41 tory T cells suppress contact hypersensitivity reactions by blocking influx of effector T cells into inflamed tissue. 

A relative of the kinases is adenylate cyclase, whose role in forming the allosteric effector 3, 5 -cyclic AMP (cAMP) was considered in Chapter 11. This enzyme catalyzes a displacement on Pa of ATP by the 3 -hydroxyl group of its ribose ring (see Eq. 11-8, step a). The structure of the active site is known.905 Studies with ATPaS suggest an in-line mechanism resembling that of ribonuclease (step a, Eq. 12-25). However, it is Mg2+ dependent, does not utilize the two-histidine mechanism of ribonuclease A, and involves an aspartate carboxylate as catalytic base.906 All isoforms of adenylate cyclase are activated by the a subunits of some G proteins (Chapter 11). The structures907 of Gsa and of its complex with adenylate kinase905 have been determined. The Gsa activator appears to serve as an allosteric effector. 

The downstream effectors of TRAF signaling are transcription factors in the nuclear factor k-B (NF-kB) and activator protein-1 (AP-1) family (Ghosh and Karin, 2002 Shaulian and Karin, 2002), which can turn on numerous genes involved in many aspects of cellular and immune functions. While the carboxyl terminal TRAF domain, containing a coiled-coil TRAF-N domain and a conserved TRAF-C domain, is both necessary and sufficient for TRAF self-association and receptor interaction, the amino terminal domain, containing RING and zinc-finger motifs, is important for downstream functions (Rothe et al, 1994). 

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