The amino-terminal helix of GM-CSF and IL-5 governs high affinity binding to their receptors.

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Abstract
Transduction of the biological effects of granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) and interleukin‐5 (IL‐5) requires the interaction of each cytokine with at least two cell surface receptor components, one of which is shared between these two cytokines. A strategy is presented that allowed us to identify receptor binding determinants in GM‐CSF and IL‐5. Mixed species (human and mouse) receptors were used to locate unique receptor binding domains on a series of human‐mouse hybrid GM‐CSF and IL‐5 cytokines. Results show that the interaction of these two cytokines with the shared subunit of their high affinity receptor complexes is governed by a very small part of their peptide chains. The presence of a few key residues in the amino‐terminal alpha‐helix of each ligand is sufficient to confer specificity to the interaction. Comparison with other cytokines suggests that the amino‐terminal helix of many of these proteins may contain the recognition element for the formation of high affinity binding sites with the alpha subunit of their multi‐component receptors.