THE EVOLUTION OF HEMATOPOIETIC CYTOKINE RECEPTOR COMPLEXES/

The evolutionary expansion of the haematopoietic cytokines and their r eceptors is characterized by the duplication of both cytokines and rec eptors. A systematic analysis of primary sequence homology indicates t hat receptors for gp130-associated cytokines group into signal transdu cing and non-signal transducing receptors. This observation is consist ent with the evolution of the interleukins 6, 11 and 12, granulocyte c olony stimulating factor (G-CSF), leukemia inhibitory factor (LIF), on costatin M, and the ciliary neurotrophic factor complexes from a commo n ancestral complex which included a homodimer of gp130-like signallin g receptors and an interleukin 6 receptor-like non-signalling receptor . Alterations in the components of the complex are proposed to have ar isen by receptor duplication and divergence to allow signal transducti on via a LIF receptor/gp130 heterodimer, and loss of the non-signallin g receptor component in the G-CSF and the LIF lineage. The short-chain haematopoietins and their receptors do not group clearly although int erleukins 4 and 13 grouped together, as did 2 and 10, Internal duplica tion of the ligand-binding domain appears to have occurred independent ly in three separate lineages. These observations have implications fo r the classification of cytokines and receptors, and for the modelling by homology of their structures and interactions. (C) 1995 Academic P ress Limited.