title: Mutational analysis of a critical signaling domain of the human interleukin 4 receptor.
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.
authors.affiliation: Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115.
authors.forename: D C
authors.initials: DC
authors.lastname: Seldin
authors.forename: P
authors.initials: P
authors.lastname: Leder
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D002460:Cell Line; D017124:Conserved Sequence; D004247:DNA; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D016133:Polymerase Chain Reaction; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D014162:Transfection
chemical_list: D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D004247:DNA