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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1994 Mar 15;91(6):2140–2144. doi: 10.1073/pnas.91.6.2140

Mutational analysis of a critical signaling domain of the human interleukin 4 receptor.

D C Seldin 1, P Leder 1
PMCID: PMC43325  PMID: 8134361

Abstract

The human interleukin 4 receptor (hIL-4R) is a member of a superfamily of cytokine receptors defined by conserved features of their extracellular domains. The intracellular domains of the hIL-4R and of other members of this family lack any recognizable enzymatic motifs, though ligand-dependent tyrosine phosphorylation of these receptors has been observed. Recent studies have suggested that serine-rich and acidic domains within the cytoplasmic portions of cytokine receptors might be required for signal transduction. Using deletion and truncation mutants of the hIL-4R, we have explored an essential 39-amino acid signaling domain that is rich in acidic amino acid residues and in serine residues that form consensus phosphorylation sites for known serine/threonine kinases. To assess the contribution of these motifs to signaling, we engineered site-directed mutants of these residues. Surprisingly, cells expressing mutant hIL-4R lacking either the serine or the acidic amino acids retain the ability of cells expressing the wild-type receptor to proliferate in hIL-4. Furthermore, receptors in which all six cytoplasmic tyrosines are absent can function, suggesting that tyrosine phosphorylation of the receptor may be an epiphenomenon rather than a requisite event in signaling.

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Selected References

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