Transmembrane and intracellular signalling by interleukin-4: Receptor dimerization and beyond

IL-4 is a paradigmatic example for hematopoietic cytokines of the four-helix-bundle family, but offers some unusual features as well. Two receptor binding sites with different properties were identified in the molecule, which has allowed the development of antagonistic mutant proteins, and contributed to the now accepted concept that cytokines signal across membranes by crosslinking two receptor proteins. Intracellular signal transduction by IL-4 involves activation of Jak kinases and a pathway with homology to the insulin system, but not the ras/Raf-cascade. Receptor/ligand interactions are complex, because IL-4 and IL-13 share the main receptor component, and IL-4 can signal via a second type of receptor on some cells.