Why Chemokines are Cytokines while their Receptors are not Cytokine Ones?

Chemotactic cytokines, or chemokines, are a large family of small proteins, which are distinguished from other cytokines in that they are the only members of the cytokine family that act on G-protein coupled receptor superfamily. This minireview tries to answer the title question by structure/function analysis of chemokines, cytokines, and their receptors. We also consider secretion of chemokines/ cytokines in health and disease as well as expression of their receptors both in immune system and brain. Our analysis suggests that cytokine and chemokine receptors may share similar architecture with Toll-like receptors. Such similarity hints a similar way of their functioning as molecular switches controlled by protein-protein interactions. Hence, we pay attention to the related receptor-receptor associations and evolutionary conserved leucine-rich motifs.