Full house: 12 receptors for 27 cytokines.

With the sequencing of the human genome nearing completion, it appears that all members of the class II cytokine receptor family (CRF2) have been identified and partially characterized. The entire family is composed of exactly one dozen members. Eleven of them combine as various heterodimers to transduce signals across the cellular membrane for 27 cytokines divided into four structurally related groups: 6 cytokines of the IL-10 family, 17 type I IFNs, 1 type II IFN and 3 IFN-lambdas. The last CRF2 member is the soluble receptor which can neutralize the action of one of the cytokines of the IL-10 family, IL-22. Although the extracellular domains of all CRF2 proteins reveal primary and structural homology, their intracellular domains are very dissimilar. Nevertheless, signaling events induced through various combinations of CRF2 subunits partially overlap, leading to the induction of overlapping but cytokine-specific biological activities.