title: Internalization and nuclear localization of interleukin 1 are not sufficient for function.
abstract: The human fibroblast interleukin 1 (IL-1) receptor is a glycosylated transmembrane protein with a cytoplasmic domain of 213 amino acids. We have constructed a series of deletion mutants of the cytoplasmic region of the IL 1 receptor and have used these mutants to examine its role in ligand binding, internalization, signal transduction, and nuclear localization of IL-1. Mutant receptors lacking most of the cytoplasmic domain are expressed at the cell surface and can bind, internalize, and localize IL-1 at the nucleus, but they do not allow IL-1-mediated induction of interleukin 2 and SV40 promoters. We have localized a critical region for signal transduction to a 50-amino acid segment of the cytoplasmic domain of the receptor. These studies demonstrate that IL-1 internalization and nuclear localization are not sufficient to trigger IL-1 activation of gene expression in T-cells.
authors.affiliation: Sclavo Research Center, Siena, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Heguy
authors.forename: C
authors.initials: C
authors.lastname: Baldari
authors.forename: K
authors.initials: K
authors.lastname: Bush
authors.forename: R
authors.initials: R
authors.lastname: Nagele
authors.forename: R C
authors.initials: RC
authors.lastname: Newton
authors.forename: R J
authors.initials: RJ
authors.lastname: Robb
authors.forename: R
authors.initials: R
authors.lastname: Horuk
authors.forename: J L
authors.initials: JL
authors.lastname: Telford
authors.forename: M
authors.initials: M
authors.lastname: Melli
mesh_terms: D001345:Autoradiography; D001665:Binding Sites; D002460:Cell Line / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D015500:Chloramphenicol O-Acetyltransferase; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D004252:DNA Mutational Analysis; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000502:physiology; D011971:Receptors, Immunologic / Q000737:chemistry / Q000502:physiology*; D017472:Receptors, Interleukin-1; D011993:Recombinant Fusion Proteins; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology; D013539:Simian virus 40
chemical_list: D007375:Interleukin-1; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D011993:Recombinant Fusion Proteins; D015500:Chloramphenicol O-Acetyltransferase