The rat interleukin 4 receptor: coevolution of ligand and receptor

Abstract A rat interleukin 4 receptor (IL-4R) cDNA was cloned by polymerase chain reaction (PCR) using RNA of Con A activated T cells and primers deduced from mouse and human IL-4R sequences. Sequence analysis revealed an open reading frame for a putative membrane protein of 800 amino acids in length. It comprises an overall identity of 52 ad 78% to its human and mouse homologues, respectively. The extracellular part of the rat IL-4R contains a number of residues including cysteines and a WSXWS motif typical for the cytokine receptor superfamily. Analysis of amino acid exchanges between rat and mouse IL-4 receptors deciphered for replacement (R) or silent (S) mutations suggested different types of selective pressure acting on the extracellular and intracellular domains. A high R/S value that indicates selective pressure for amino acid exchanges was found for the extracellular domain and a low R/S value for the intracellular part of the IL-4R. Since we previously found a similar high R/S value in the rat IL-4 gene encoding the ligand for the IL-4R, the high amino acid exchange rate can best be explained by coevolution between IL-4 and the ligand binding domain of the IL-4R to improve or retain affinity.