title: Function of a conserved residue in the amino terminal alpha-helix of four helical bundle cytokines.
abstract: The Glu residue in the helix A is conserved among many cytokines. Mutation in this residue converts some cytokines to an antagonist. Such an artificial cytokine with an antagonist activity may be useful in a clinical area. In this study we generated a mutant granulocyte colony-stimulating factor (G-CSF) termed G-CSF.E20K in which this residue is substituted to Lys. It is known that G-CSF binds to a homodimeric receptor, while other cytokines which can be converted to antagonists bind to heterodimeric receptors. We showed that G-CSF.E20K does not bind to the receptor at all, and that it fails to stimulate proliferation. Thus, the mutant did not act as an antagonist. We propose that the nature of the receptor, namely whether it is a homodimer or heterodimer, determines the antagonist activity of the mutant.
authors.affiliation: Department of Clinical Pharmacology, Jichi Medical School, Tochigi 329-0498, Japan. oshima@jichi.ac.jp
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Oshima
authors.forename: Akio
authors.initials: A
authors.lastname: Fujimura
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D016207:Cytokines / Q000378:metabolism*; D019281:Dimerization; D004285:Dogs; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein
chemical_list: D000596:Amino Acids; D016207:Cytokines; D016179:Granulocyte Colony-Stimulating Factor