title: Generation of secretable and nonsecretable interleukin 15 isoforms through alternate usage of signal peptides.
abstract: Two isoforms of human interleukin 15 (IL-15) exist. One isoform has a shorter putative signal peptide (21 amino acids) and its transcript shows a tissue distribution pattern that is distinct from that of the alternative IL-15 isoform with a 48-aa signal peptide. The 21-aa signal isoform is preferentially expressed in tissues such as testis and thymus. Experiments using different combinations of signal peptides and mature proteins (IL-2, IL-15, and green fluorescent protein) showed that the short signal peptide regulates the fate of the mature protein by controlling the intracellular trafficking to nonendoplasmic reticulum sites, whereas the long signal peptide both regulates the rate of protein translation and functions as a secretory signal peptide. As a consequence, the IL-15 associated with the short signal peptide is not secreted, but rather is stored intracellularly, appearing in the nucleus and cytoplasmic components. Such production of an intracellular lymphokine is not typical of other soluble interleukin systems, suggesting a biological function for IL-15 as an intracellular molecule.
authors.affiliation: Metabolism Branch, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA. ytagaya@helix.nih.gov
authors.forename: Y
authors.initials: Y
authors.lastname: Tagaya
authors.forename: G
authors.initials: G
authors.lastname: Kurys
authors.forename: T A
authors.initials: TA
authors.lastname: Thies
authors.forename: J M
authors.initials: JM
authors.lastname: Losi
authors.forename: N
authors.initials: N
authors.lastname: Azimi
authors.forename: J A
authors.initials: JA
authors.lastname: Hanover
authors.forename: R N
authors.initials: RN
authors.lastname: Bamford
authors.forename: T A
authors.initials: TA
authors.lastname: Waldmann
mesh_terms: D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D006801:Humans; D019409:Interleukin-15 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015202:Protein Engineering
chemical_list: D019409:Interleukin-15; D010455:Peptides